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How Does The Leptin Rx Work?


Readers Summary

  1. How does The Leptin Rx Work?
  2. Do we have alternative pathways that leptin used to use?
  3. Why is leptin and light yoked?
  4. Does timing matter more than macro-nutrients in a leptin reset?

Many people have contacted me about “why” the leptin Rx works and “how” does it work.  Many people in the blogosphere have made some claims that much of what is in the leptin Rx is a rehash of the work found in some diet books.  Well, today’s post is being done to show you the science underneath my recommendations were formulated and made.  None of the underlying science I will mention to you about neuroplasticity will be found in any diet book mentioned in any blog post that I know of.  Most of you know I am a neurosurgeon, and as such, I was dramatically influenced by two world famous neurosurgeons named Wilder Penfield and David Kline.  Dr. Penfield was the first neurosurgeon to use electrodes on the brain to map it prior to surgeries to avoid neurologic damage during tumor removal.  Dr. Kline was and still is the pre eminent world expert in peripheral nerve surgery.  I happened to train with Dr. Kline in New Orleans, and got turned on to his work, Dr. Penfield’s work and the work of Dr. Merzenich in the early 1990′s before leptin was even discovered.  Dr. Michael Merzenich work on sectioning the median nerve in the hand and seeing how the brain remapped its sensory territory in the cortex via micro-electrodes was brought to my attention by Dr. Kline while I was a resident.

The Leptin Rx basis was made by a lot of reading by me in the past twenty years in multiple disciplines of science.  The biggest contribution to the leptin Rx genesis came from the work of two Nobel Prize winning teams in 1981 (David Hubel and Torsten Wiesel) and in 2000.  The Nobel prize in each case was awarded for work on neuroplasticity.  I was further influenced in 2009, when the Nobel Prize was given to Elizabeth Blackburn on her work on telomere biology.  It was further given even greater meaning by the work of Dr. Michael Merzenich on how dynamic the brain was in his brain mapping experiments after peripheral nerve injuries to the hand.  I have also mentioned Dr Luis DeLecea (sleep researcher) and Dr. Myers (world leptin expert)  works also many times in my blog about leptin.  One could spend close to a decade reading what these scientists have given us in the literature.  Their work was the foundational building blocks of the Leptin Rx.  The works of these giants showed us that the brain is not hardwired for life, and is in a constant state of flux given the inputs it does receive and can interpret.  When we continuously use a brain circuit, it is favored by its overuse and eventually is learned to be relied upon as the defacto center of this function.  In this way, as a human ages, certain parts of the cerebral cortex become specialized for certain functions.

For example, if a child learns two languages fluently before the age of six,  they will be able to learn not only the language but also the accent of the native tongue.  This age of 6 will be really important when we get to speak about myelination and autism.  If the child learns two languages later in childhood, they can learn both languages,  but the newer language will not be learned with any accent because the dominate language filled that receptive field in the brain that wires for accent already.  The same is true for adults who learn a new language in later life. This appears to play a role in how we hardwire our brains and its epigenetic signals for foods as well.

Back in the 1930′s, the world believed that the brain had localized areas of eloquent functions that were fixed in position for life.  Dr. Penfield’s work revealed slowly that the belief of localization of function was not hardwired but dynamic.  He never became famous for showing how we could adapt brain functions because this was not his goal as a neurosurgeon.  It was to avoid eloquent areas to avoid neurologic damage to a patient during a surgery.  The extreme adaptability of the neural pathways was shown by Dr. Merzenich work from the 1960- to current day.  His research has allowed us to take deaf people with destroyed cochlea’s and allow them to hear again by retraining lesser used auditory cortex to learn via an external micro-electrode array placed upon the brain.  25 years ago this sounded crazy.  Today we now have life long deaf people learning to hear for the first time.  When I read about his work, 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.  It is critically important in gut dysbiosis and obesity generation as well.  Cyberonics is a company that began making vagal nerve stimulators when I was in my residency to treat seizures.  I remember Dr. Kline asking me to look at this technology back in my residency and thinking how bizarre it was to place a peripheral nerve stimulator on a cranial nerve could treat seizures.

When Dr. Kline forced me to learn about this stimulator, it made me realize that we did not have to have an external stimulator to reset or reteach a damage neural circuit, if the afferent arm of the neural circuit was functioning normally.  In the case of seizures,  the vagal nerve was totally normal in all cases.  When I read more deeply about how the stimulator worked, I realized that this could also help people with hypothalamic obesity from surgery or from radiation damage as well.  These were conditions were people were losing energy to the environment.

Simultaneous to this, leptin was found in 1994 and research began to pour out about this hormone and receptor in the obesity literature. I also found out that Cyberonics was planning on using their vagal nerve stimulator in obesity trials.  Those of you who attended the AHS will remember that I specifically asked Dr. Robert Lustig a question about the vagal nerve stimulator and  “his theory” on how leptin fit into the genesis of metabolic syndrome at UCLA this past August.

The Leptin Rx is my version of how to retrain the hypothalamus to account for the electrons and photons from food that are delivered to the mitochondria.  I do this without using any electrical stimulator, because the vagus nerve and the patients light perception pathways are intact in most people who I employ this on. 

Interestingly, the leptin Rx will not work well in people who have had previous gastric surgery ( vagotomies for ulcer surgery) or gastric bypasses that destroy the normal neural connections of the gut innervated by the vagus nerve.  People with lap bands, however, it seems not to bother much because the vagus nerve remains mostly intact in these cases.  My belief is that those people who had a formal gastric bypass will need deep cold thermogenesis, an external vagal stimulator, and/or synthetic leptin to get to optimal once again.  It will work in blind people because the light perception pathway is not 100% visually mediated so circadian timing can be relearned to meal timing.  Neither of these things are currently approved treatments, but both are being researched today.  That is why I am so anti gastric bypass,  in case you were wondering.

I learned empirically, the mitochondrial response of this neural retraining, could be followed and accounted for by the neuro-humeral response of the brain.  This means that energy balance is codified in our hormone panel.  That means the patients hormone status could be used as a detector to see how the system went awry and how it was responding to retraining over time. This was the most labor intensive time in synthesizing what I had learned about leptin.  When I had I thought I had it all worked out in my own mind and in my notes, I became the guinea pig for this thought experiment.  I used quarterly labs to test what I had learned by following my own diurnal rhythms.  I wrote down a lot of thoughts as time went on.  I went back and got extra training on neuro-humoral chemistry and endocrinology when I got lost.  I read a lot of papers and books.  The entirely of these works also showed that completely damaged parts of the neurologic system can be reconstructed by teaching the brain how to use lesser used or unharmed  neural circuits to replace the damaged hardwired circuits the organism was adapted to and relied upon.  This is when I began to synthesize the leptin Rx.  I have never spoken of how I came up with this, because it is very complicated and drew from many areas of science, especially quantum physics.  You asked me to blog about it,  so here it is for you to read.

Now,  on to the neuro-humoral significance of the Leptin Rx.  Why did I choose to use protein and fat to retrain the brain?  Because carbohydrates are coded for in the brainstem by a neuropeptide called neuropeptide Y (NPY).  Altering NPY is easy via the diet and by timing. It appears our biology is adapted to realizing that excess carbs in our environment tend to show up only when the light cycles are long as well. Carb intake is also tied to the controller (dopamine) of the releasing hormones of the pituitary and to the light cycle.  So the choice was pretty easy considering how the brain accounts for carbs in these two ways.  What is the significance of the prolactin control or surge you ask?  The significance of the prolactin surge (especially in older people) is made clear if you eat carbs within 4 hours of going to sleep.  Prolactin release is yoked to the dark/light conditions in most mammals. If you do not think prolactin is important for a natural sleep cycle watch this 4 minute TED video.  It is also tied to NPY and to inflammatory cytokine signals in the brain.  If you eat a large amount of carbs after dark it is spikes NPY, IL-6, TNF alpha, and raises sdLDL release at our liver.  This has multiple effects on the system.   The sdLDL blocks the ability of leptin to enter the hypothalamus at its evolutionary appointed time, 4 hours after you last eat or 4 hours after darkness falls. Il-6 and TNF alpha block the effects of leptin in the brain, liver and at muscles. The more carbs one eats, the higher NPY levels remain in the brain as well and this causes the carbohydrate cravings that most people report when they are leptin resistant.

These findings are all adaptable by the brain as light levels change as well.  The evolutionary reason for this is that carbs were not available in most places as winter fell because of growing season changes.  This would be more pronounced as one moves from the equator, and less pronounced closer to it.  The circadian rhythm of vitamin D levels is also accounted for to judge light levels as well. Those closer to the equator would have much higher levels of Vitamin D and would be able to account for a higher carb level they face. Many current day leptin resistant folks find out their vitamin D levels are low when they finally test for it. We are best adapted to eat carbs in high light conditions and not in low light conditions, and this is why leptin is signaled at low light conditions in the brain. Its not magic its evolution at work. This is also the reason why I want my Leptin Rx patients supplementing with D3 to optimal levels and limiting carbs when they are trying to lose weight.  This input radically causes the hypothalamus to reorganize based upon the new sensory “non leptin” signals and not rely on the newly adapted leptin receptors in the damaged hypothalamus.

It is time to get back to Prolactin secretion, and how our circadian rhythm works side by side with the leptin receptors in the brain.  Prolactin plays a huge role in setting the system up via our circadian rhythms. The first step in the process is leptin levels rise slowly for fours after our dinner meal, and the second phase of insulin released is completed and over.  This generally occurs by midnight in a normal person.  At midnight, leptin then should enter the hypothalamus and bind to its receptor.  Once it binds to the leptin receptor two things occur.  The first is a second messenger is sent to the thyroid gland to up-regulate the  T3 production.  Increasing T3 then  stimulates the uncoupling protein 3 in muscles to burn fat liberated from our fat cells as we sleep.  So we are designed to lose weight as we sleep.  This is how the brain regulates calories intake and excess.  Leptin raises our metabolic rate during the first two stages of sleep.  If one has a sleep disorder, this will not work.  This is another way leptin and sleep are coupled.  The fats liberated from adipocytes are then burned both as energy producing ATP to drive repair programs in sleep, and they are burned to free heat at UCP1.  If one is LR, you cannot do these things.  This is why calories don’t really matter when one is leptin sensitive and matter a lot more when one is leptin resistant.  Hormones completely control how we account for calories.  If you remember reading the Leptin part three blog, fat burning requires leptin sensitivity and proper thyroid function at the muscle level for this to occur.

The second effect is via another second messenger.  The leptin molecule and receptor bind, and sends a message to the anterior pituitary gland to release prolactin from 12-2 AM while we are in the first few stages of sleep.  The prolactin release is required for proper control of all 4 sleep stages and this effectively yokes sleep and metabolism at the hypothalamic level.  The real benefit is  the signal the hypothalamus uses to release growth hormone in a pulsatile fashion from from 2 AM to 5 AM during sleep stages 2-4.  Growth hormone release  allows the process of autophagy to be at maximal efficiency as we sleep. Recall that autophagy is the process of cellular renewal. In autophagy, we recycle proteins, we hardwire new behaviors and circuits we learned, and retool our brains from yesterdays oxidative damage. To do this well requires good sleep and optimal leptin function.  People with sleep apnea have some of the lowest levels of growth hormone measured and this helps partially explain why most of them have body composition issues.

People who have sleep apnea, are generally obese.  This is true in 80-90% of cases.  After reading the science above, it should be clear to you why this happens now.  The 10-20 % of sleep apnea patients who are not obese get it because of high inflammatory cytokines that occurs  from other etiologies.  Remember that obesity cause inflammation itself, and this is why one becomes leptin resistance most of the time.  This is why I use HS -CRP as a major clinical marker of a person inflammatory status.  The underlying cause of sleep apnea is usually due to high levels of IL-6 and TNF alpha.  The clinical measures one can use to assess this is a history from the patient of insomnia with daytime sleepiness and a general lack of energy.  They also will report significant muscle pain with exercise.  Often they have low CO2 on chemistry testing as well.  Often when the sleep disturbance is the most prominent physical finding or complaint I will check a DHEA level.  DHEA levels correspond very well with high IL-6 levels (98% correlation).  Testing for IL-6 is very expensive and therefore is not commonly done.  DHEA levels are very commonly done and much cheaper to do so that is why I lean on this test more than a formal cytokine panel.

Leptin resistant patients never get their pulsatile GH release at 12-2 AM, and as a result of this lack of growth hormone release,  autophagic repair is poor in them.  This means that they cannot recycle and repair their normal cellular damage from the daytime and this further degrades their ability to be energy efficient at their mitochondrial level.  When this occurs chronically,  poor autophagy can eventually cause neolithic diseases we commonly see in aging.  These patients suffer more chronic diseases and age faster because their sleep is uncoupled from their metabolism.  This is why sleep is restorative, and why evolution seems to have coupled sleep and energy metabolism.  If you remember from the Gnoll’s post I spoke about how magnesium is a co-factor in ATP production at the mitochondria.  In people who have poor sleep or poor metabolisms (think Sleep Apnea or T2D) they also have other sleep disorders that are also tied to lack of magnesium due to the loss of intracellular water.  One great example is the “restless leg syndrome.”  Restless leg syndrome is on a “disease continuum” with sleep apnea and just represents an earlier symptom of a brewing energy inefficiency problem.  When a patient presents with these signs in their history,  it is a tip off to the physician that there is a significant underlying metabolic disorder ongoing at the mitochondrial level.

It then follows, when the mitochondria are involved,  leptin functioning is also not optimal because both are linked at all physiologic levels of energy production.  The most important point is that this energy inefficiency is then directly translated physiologically to our telomeres.  Our telomere lengths determine how long our cells live normally, become senescent, or become diseased and are forced to go through cell suicide (apoptosis) or become oncogenic.  This is why metabolic and diseases of aging are linked together.  This is why T2D’s have more AD, more risk of heart disease, atherosclerosis, stroke, and cancers as they age.  The biologic message of inflammation at our mitochondrial means we age faster and die sooner of some neolithic disease.  The diseases we get or die from are largely due to a combination of what our epigenetic receptors sense  on a daily basis from all of our metabolic pathways that converge on the mitochondria.  The key to healthy living is to pay great attention of what lifestyle changes are ideal for your mitochondria.  Most people will find the evolutionary life style advocated by books like the Epi-paleo Rx, are generally are ideal to meet these goals.  I believe your leptin status is the golden key to unlocking how it all is coupled.

When someone is not responsive to the receptor signaling of leptin in the hypothalamus, they become unable to burn their excess energy off as pure heat so they remain overweight. The reason is simple.  They do not have any excess energy to burn as you will find out.  They find it very difficult to lose the weight, even when they restrict calories to starvation levels.  This will change when they become leptin sensitive once again.  Some obese people appear to do tremendous damage to their leptin receptors and need synthetic leptin to continue to lose or maintain their weight loss.  We realized this in the results of Amgen leptin trials data.  Moreover, some of these people have found that removing adipocytes surgically also helps them maintain their weight better as well.  Long term studies need to be done on these people to see if surgical removal of fat is really necessary for long term weight control, or can long term neuroplastic training be done while the hypothalamus undergoes neuroplastic repair over time.  In my opinion, I think if we use timing of meals and couple it to the day light cycles as they adjust daily,  we can facilitate that neuroplasticity.  This is really the science behind the Leptin Rx.  I have read extensively about the work of neurosurgeon and neuroscientists Penfield, Paul Bach y Rita, and Merzenich and their experiments have proved that the brain is very plastic, and can be retaught how to work optimally again if we give it a “new way” to perceive a stimulus once damage to another part of the brain has occurred.

We can achieve leptin sensitivity after the hypothalamus is damaged, if we teach the brain how to use our older evolutionary non-leptin neural circuits.  Yoking eating to light and day, and making timing to sleep and wakefulness and to the visceral sensations of distention of the gut via the vagus nerve are precisely how the Leptin Rx is designed to work.  Taking full advantage of how certain macro-nutirents are tied to light cycle further helps reset hypothalamus in two to three months.  The more inflammation that is present, the longer the reset may take.  Instead of relying on optimal functioning of the hypothalamic leptin receptor, we can re-teach the hypothalamus to pay attention to the light levels, awakening time, time we sleep and face dark, when our gut is distended and filled with food and when it is not.  We can also load the diet with protein and fat at certain times, to take full advantage of the existing working neural circuits in the brainstem and hypothalamus that accounts for carbohydrates,  to our advantage in resetting how the brain can more fully perceive our energy status when the leptin receptor is not functioning.  This science is precisely how a cochlear implant works in a neural deaf patient.  It is not opinion, it is merely applying what we know works in one part of the brainstem, and using it another part using the natural circadian rhythms to allow the brain to re learn how to account for macronutrients correctly once again.  It is also how neuroscientists have taught blind people to see using their tongue or tactile skin receptors to read (Paul Bach Y Rita work and braille as examples).

When the leptin receptor is not working well ,we can try to bypass it by using other neural pathways that leptin does also monitor but rarely uses any longer. This retraining allows the brain to relearn perception. The experiments of Dr. Merzenich cutting the median nerve completely and seeing the brain re map its sensory territory opened my eyes to this possibility.

When we eat meals, the sensation of physically eating is perceived by the vagus nerve.  This nerve controls the entire GI tract down to the transverse mesocolon.  It also monitors the hypothalamic parotid axis in the mouth that monitors carbohydrate contents in food in the mouth. This signal is an early detection system for the incretin gut hormone (ghrelin, PYY, CCK, agouti, glucagon) system that readies the gut for digestion.  If one eats with a certain regularity (Leptin Rx) and makes sure it is tied to the sleep wake cycle, we can retrain the brain to account for food using older evolutionary pathways. The leptin receptor in the hypocretin neurons are newly adapted evolutionary speaking compared to the ones that rely on circadian signals. This  has been demonstrated in Dr. LeCea’s work on sleep and leptin in narcolepsy.  Leptin function, however, is found widespread in the animal kingdom, and has been used for long periods of time in evolution.  The difference for humans today is how our neural circuitry has evolved to incorporate the leptin receptor for use in our brain to accounts for energy status.  It appears we humans still have the “old wiring diagrams” in place, but we don’t use it these days because we evolved a “better” mechanism to account for food electrons from macronutrients. Moreover, it appears that today’s standard American diet causes a mismatch in how the currently evolved leptin receptor works over time.  These new receptors are mismatched to our current diet and can cause our leptin receptor to fail when the signaling is overwhelmed with inflammation.

We are adapted to use the new system because of the positive reinforcement of these tracts from 0-6 years old.  This hard wiring is not set in stone for a lifetime. But we rarely use it past this age. It becomes the preferred neural circuit because it is used chronically while the alternative pathways are not reenforced. It is analogous to how humans code for languages as I mentioned earlier. I think that should help many understand why I mention the age of six as being a huge factor in setting how we partition energy epigenetically. Once the leptin receptor is not able to pick the signal up correctly major intracellular magnesium changes begin in our cells of our pancreas, liver, and our muscles to compensate.  Energy status changes protein structure just as it does in the core of a star.  When this occurs over years, we eventually wind up seeing the metabolic syndrome and the development of a variety of diseases of aging. Once we re-engineer the hypothalamus, we can then feed it a non inflammatory ancestral diet and get on to the business of optimizing ourselves once again.

We should now get back to discussing the neuro-humeral response of the brain to leptin; Timing is more critical than any other factor in the Leptin Rx. The reason for this is we are using multiple circadian cycles to reset the hypothalamus when it is flying blind due to brain inflammation at the receptor site. When we eat our last meal of the day as light levels begin to fall, leptin needs a minimum of four hours to be able to act on its receptor to signal the brain to our current energy status. The reason for this appears to be the biphasic insulin response from our last eaten meal, namely dinner. Any spike of insulin blocks the ability of leptin to enter the hypothalamus to give the brain this signal. This is why I tell you not to snack post dinner at all. Once leptin binds to the receptor, it then blocks dopamine’s control over the releasing factors in the pituitary.  Pituitary prolactin secretion is regulated by dopamine to act on the dopamine-2 receptors Prolactin cells, causing inhibition of prolactin secretion.  Once leptin binds, it blocks this inhibition and allows for prolactin to be released and to act to release growth hormone.  Prolactin is the trigger for growth hormone release in humans. 90% of a humans growth hormone is released during sleep, if prolactin is allowed to act. Women in menopause have major prolactin releasing problems, and this is why they have sleep complaints, and why they get more belly fat at this point in their life. GH decreases abdominal fat while simultaneously increasing your lean muscle mass. It does this by increasing  protein synthesis for renewal during autophagy.  This is the hormone responsible for body composition in large part with the sex steroid hormones.

If you have a bad body composition, you can bet that you have a leptin problem and a quantum sleep issue. This is why the mirror test works in most cases without testing. GH levels fall off a cliff for most women after age 40 (peri-menopause) and for men after age fifty. Any increase in inflammation for any reason generally makes menopause or andropause happen more quickly. When this happens, there is a corresponding drop in the quality of sleep as well the amount of autophagic repair. This is why I always ask a patient about sleep. It is a cardinal sign of a serious metabolic problem at the brain level. This reduction in autophagic repair is why people age and why disease increases as we age too.  These biologic facts are widely reported in the literature.  This is why older people tend to sleep less than younger people.  It is also why babies sleep so long.

Infants are growing, myelinating, and learning, and require more autographic repair as they trim all their newly laid down hard wired tracts.  Babies release a ton of GH as they sleep to grow and evolve to get everything working optimally in their brain and in their immune system.

Older circadian rhythms were most important before mammals had the leptin receptor in their brain working as it does now.  They used it to adapt as the light/sun changes with seasons.  Light is part of the electromagnetic spectrum.  Humans still have this ability, but it goes unused because it is not selected for as we live and grow in today’s modern environment. We evolved past these more primitive systems, but they still work within us,  if we exercise those circuits. With changing light levels, our pituitary is still capable of controlling energy metabolism if we teach it how to do so.  Pituitary secretion has been shown to adapt to light and to new circadian cycles in humans as well. When I learned about these methods and married them to what I new about the vagus nerve control of the gut, I came up with some “exercises” to re train my own hypothalamus.

These biological facts have allowed me to reset many people’s hypothalamus over the last 6 years to use alternative pathways to account for the electrons we use to make ATP from food. It helps to restore proper brain signaling when our newer, more adapted systems becomes resistant to normal dietary signaling.  As light levels change your diet should too, in my view. In our world, today it does not. Interestingly, exercise is more efficient in cold temps and low light conditions, as well because you activate both UCP1 and 3 if you are LS and thyroid is working well. That is also why I like training in low light conditions prior to bed. It also helps abruptly end the insulin spike of eating and readies the brain to accept leptin into its normal receptor binding area. It also allows for fat burning at the muscle levels to occur far in advance of what will occur when leptin acts on the brain later to do the same thing. This is why so many people report dramatic weight loss from night to day. I still tell people not to scale watch, because it increases your cortisol which slows weight loss down. It appears that exercising also has a circadian leptin Rx.  That will be the feature of a later blog in the Quilt.

I hope this explains how the leptin Rx works for humans.

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Additional Resources

  • My Leptin Prescription http://jackkruse.com/my-leptin-prescription/
    What Are The Optimizing Labs? http://www.jackkruse.com/what-are-the-optimizing-labs/
    The Leptin Rx: FAQs http://www.jackkruse.com/the-leptin-rx-faqs/
    Leptin Reset http://www.jackkruse.com/easy-start-guide/
    Gnolls.org Opens The Door To Obesity Fight http://www.jackkruse.com/gnolls-com-opens-the-door-to-obesity-fight/
    The Quilt http://www.jackkruse.com/the-quilthow-to-beat-agin/
    The “Teeth” in Disease? http://www.jackkruse.com/the-teeth-in-disease/

Cites

  • Google scholar any of the mentioned researchers names and be prepared for ten years worth of links on this work. It will keep you quite busy.

 

Comments

  1. Thanks so much for this. This really helps me understand better what you have been saying. Now I need

    to get my thyroid up to par and buckle down on the reset.

  2. As winter approaches and the mornings darker, will this have an effect on the timing of b/fast?

    • @PhilT It will if you follow the circadian cycle. Most people will notice a sleep change who are trying the reset as the time shortens as we head to winter in the northern hemisphere. It is more noticeable if you have a poorly functioning thyroid too. The opposite is true for my friends in the southern hemisphere. I am a huge stickler about Vitamin D levels being great by Sept 15 in the northern hemisphere. I also alter my sleep wake cycles and cut my carbs bigtime in winter time. I also work out close to naked and with ice on my back as the weather gets colder. In summer I don't lift or work out as hard either. I try to work with my evolutionary biology and not mismatch to it as much as I can. My food choices also generally change as well. I have learned all this from serial testing of my own blood. It may not be for everyone but I know what works best for me. This is why I have a huge issue with many folks who just advocate eating a paleo diet and living a paleo template. I dont think that gets most people to optimal. I believe in quantifying myself with testing to find out what is really optimal for me and my patients. No one context is right for anyone. This is what I really learned most from this.

  3. WOW, thanks for the in-depth explanation of the Rx. It's been working for me and I'm grateful that you have shared your knowledge and experience.

    • @Melinda Thanks for the kind words. I honestly did not think anyone would care how I came to work around a "broken signaling" system in the brain. Many people have complained that my writing drives them nuts so I figured a detailed blog of the neuroscience that I have experienced over the last twenty years would bore most to tears. Much of the science is very detailed and not at all tied to hypothalamic function. It however was instructive of exactly how our brain works and adapts to selective pressures and learning. When I wrote this blog it was four times as long as this copy. I cut all the science and links out.

      A scientist lives by their hypothesis and their experimental results.

      A doctor is a maven who melds that science with the art of healing to improve your former self without harm.

  4. Very interesting article which really makes sense. Since I've been trying the RX my sleep has changed beyond recognition; I'm actually tired at night time – and wake up before my alarm!

    • @Suz glad to hear it and thanks for the kind words. I wish I was in your hemisphere now……I already miss summer.

  5. Thanks! I’ve been wondering about this for a long time, and now that you’ve explained it this way it will make it that much easier to do the protocol.

    On top of that, it’s fascinating! :)

  6. I have obstructive sleep apnea and have used a CPAP for 7 years, I became obese. I have been folowing the Primal Blueprint for 1 year and have lost over 50 lbs (from 225 to 175, 5'10, 46yo male). I see all the signs of restored leptin sensitivity and feel great. The past few months, I find myself waking up around 3am after 4-5hrs of sleep, and tossing and turning the rest of the night. Before paleo, I would sleep til the alarm went off and still not feel rested, once I lost a bunch of weight, I would wake up 10 minutes before my alarm went off at 6am, feeling well-rested and ready to go. Is this a common progression of sleep patterns after regaining LS?

  7. You say 'as light levels change your diet should too'. But how? Timing? Amount?

    • @Kathy the answers completely depend upon your hormonal response to nutrients. I only make changes based upon people who test serially. This is why I dont talk about it much on the blog. I have no context to work with there. I can tell you what I do but that is based upon how I partition calories and how circadian cycles work with my biology. This is why I think talking about Kitavins and Masai and making generalizations is utterly useless. If you are a Kitavin great. No one I know shares their biology.

      I'll give you another example that Taubes and Guyenet spoke about briefly at AHS. They talked the PIMA indians and their struggle's with T2D (90% have it). Neither one however spoke about the Mexicans who live across the border who live a very HG lifestyle and who are indigent and share the PIMA'S epigenetic lineage……..none of them have the PIMA'S problems. To me that is very instructive of where the real problem lies. They are genetically related and eat and live completely mismatched live to one another.

  8. Interesting. So the circadian system was the Ur-energy regulating system, then leptin, and then reward?

    And our modern diet breaks the reward system, but does it break the leptin system? Or is the leptin system just overwhelmed with too many signals for obesity.

    A great focus on sleep. I find saunas in the evening make me sleep like a baby.

    • @Charlie our current diet in the western world is a full assault on evolution and how we are designed to live. Reward theory is just the outflow tract of the entire process. This is why as a neurosurgeon I completely dismiss reward as the dominant cause of obesity. I think it plays a big role in several areas and this post touched on the dopamine issue a bit. But here is the real problem with reward theory…….if it was dominant…….we should see tons of brain tumors in this area causing massive obesity and we dont. We see it commonly in the hypothalamus.

  9. Ok, I'm rubbing my 2 working brain cells together to see if I can figure out how this applies to my 51y.o. brother's sleep problems & immune system deficiency resulting from DX of benign pituitary prolactimoma. Not so much weight problems as lifetime short sleep cycles & weak resistance to colds & flu due to weak immunity.

    I recommended the usual low carb, avoid trans fats & processed "food" diet, magnesium & such that you write about but not much compliance on his part as he thinks I'm a dumb ass. I don't dispute that generally, but is there anything outstanding you see that his specialist may have overlooked following the current 'shrink it with drugs first, surgical intervention second' protocol?

    And thanks for all you have done & do, this Bud's for you.

  10. This post was really excellently written Dr. K. Keep it up.

    • @CB Thanks. You all asked for it and I felt compelled. Just be glad I edited it down. It was close to 15,000 words initially.

  11. Once again, very nice!

  12. Thanks for yor response, Jack. I've been trying to form a 'plan' by reading your blog and following the comments- both here and the MDA thread. I'm just frustrated that there are so many variables. Even if I 'tested myself serially' I'm not sure I could come up with a working plan without a whole lot more information. I can only go where I'm led, which leaves me stuck with that paleo template.

  13. Doc,

    Thanks for the great and thorough writeup. Having spent a ton of time reading about this stuff myself, it’s interesting and enlightening to see how your professional “path” has brought you to truly understand the complexity of central regulation of metabolism. I’m far newer to this stuff than you but am amazed as I learn more. The complexity! I was also interested to read your comment above about your personal seasonal fluctuations in diet and activity (and, of course, sun exposure), as we’ve been developing some material working with this subject. Would love to run some ideas by you sometime. Thanks again for such information-dense stuff. We dig it.

    Dallas & Melissa

    • @Dallas and Melissa You can contact me anytime here, email or send me a message on twitter and I will give you my cell.

  14. Thanks for this explanation, I'll need to review it more to really understand. I've had so many requests for help with diet and fitness advice lately despite my repeated pointing out of my lack of credentials. I direct my fellow firefighter to your blog, but they're so burned out on research that I've been forced to act as a guide or educator. I have designed my whole plan for these folks around the Leptin Rx (stole it, really).

    I will be sure to pass along the success stories that are sure to result. If it is possible, can I contact you for any specific advice?

  15. Great job Dr. Kruse. I too am actually tired each night prior to going to bed, I used to have insomnia issues. My question is, if your Leptin Rx is bypassing the leptin system and using older circadian systems because leptin receptors in the hypothalamus are mired by inflammation, is there no way an obese adult can reverse that inflammation to fully restore the leptin's signaling? Or am I to understand that an obese adult will have some degree of leptin dysfunction at the hypothalamic level even after following a Paleo Diet?

  16. In other words, through the Leptin Rx, can we ever restore our body to the point where we CAN rely on the leptin system once again for calorie accounting? I'm sure if I go back to a Western diet and lifestyle, I'll become obese again within several months.

    • @Dan At this point my speculation is that we can retrain the hypothalamus. I feel I have done this to myself and many of my current patients but no one else is doing this. I have contacted Amgen about this angle and their synthetic leptin trial data but my dealings with them lead me to believe they have other plans for their synthetic leptin. I have spoken to several people in SD who were in their trial and they all had their synthetic leptin discontinued and they opted for belt lipectomies and liposuction to reduce their adipocyte numbers to control their weight. Most plastic surgeons wont do the surgery for this indication because they dont believe it is a weight loss strategy, but most plastic surgeons also think the number of fat cells we have is fixed at birth which is also old school CW. This is a research topic that probably will never get studied until synthetic leptin is FDA approved which I dont see happening anytime soon.

  17. Thanks for the info! I have obstructive sleep apnea, hypothyroid, and so much else. After losing 38 lbs over the last year, I started the Leptin Rx, and have been doing well on it. I still have about 30 lbs to lose. I use a CPAP machine and was hoping that someday I could wean myself off of it? I actually gained 20 lbs after the sleep apnea dx and going onto the CPAP machine, boo. The doctor who prescribed it said I would probably have the sleep apnea regardless of my weight, something to do with the size or condition of my throat? I hope that's not really the case! I was a good sleeper until close to menopause, and I sleep well now with the machine. I'd sure like to be able to get off it and also get off my thyroid meds (T3).

    • @LisaAPB small throat could be cause of the obstructive apnea. That is part of the 20% not caused by obesity. Oral cavity, Jaw and face abnormalities are other causes.

  18. Something else I wanted to ask about: on the hcgdietinfo forum, in one of the Leptin threads, we noticed that a great number of us have October/early November birthdays. Do you think that birth month has anything to do with whether or not a person becomes overweight? The only things I could think of is that pregnant women who deliver in those months, might consume a lot of fruit carbs in the last trimester. Or, babies learning to self feed around 10-12 months old might be given a lot of fruit because it's in season. I dunno, just thought it odd that so many of us had birthdays around this time of year.

    • @LisaAPB Ironically I am researching time of the year births and leptin levels and how it effects oocyte selection. Not sure of a link yet but it is plausible and why I am researching it.

  19. Doc, this is a fabulous post! Could you clear up something? I do not believe in calories in/calories out. I watch my carbs but I do not count calories. And will not! LOL I could go on a rant about it. I've never seen you tell anyone to count calories while on the leptin reset yet you've said calories matter when you're leptin resistant. What exactly do you mean by that? Do you mean that you DO want people to count calories or just that the type of calories matter?

    But I'm not counting them even if you tell me to! LOL I will disobey you for the first time.

    • @ Colleen It's simple. If leptin is "broken" and cant account for calories they matter then because the brain has no way of accounting for them. This i swhy fat people overeat. Their cravings are no longer under control of leptin and NPY and ghrelin and agouti run hog wild. When you regain leptin sensitivity if you eat more than you need you can rid yourself of the excess when you sleep by burning at UCP3 or by exercising in the cold by using UCP1 Both these uncoupling proteins require leptin and a good thyroid function to work. If they are not working you aint burning squat……and hence calories then matter.

  20. Cú Chul says:

    so it looks like staying in darkness from sunset 'til sunrise, or at least until sleep is done, is key. i am always tempted to read myself to sleep or to look at the computer at times like now when i cannot sleep.

    • @Cu I am probably the biggest stickler personally when it comes to the light metabolism cycle. My diet changes massively after Sept 15. And I always make sure my D levels are north of 60 by that day. If you read my Vitamin D blog you will see that there. Now you know why!!!

  21. Hmm. I got a morning measure of GH at 0.2mIE/L (09:00) (ref normal range <11mIE/L). I got a body composition problem, and wake up a lot (often at the same hour). Lost 80 pounds – last 40 won't leave…

  22. In today 's New York Times http://www.nytimes.com/2011/10/27/he…r=1&re…

    In an Australian study participants lost an average of 14 % of their body weight. After weight loss leptin levels fell by 2/3; a year later they were still 1/3 below normal. This caused increased hunger, leading them to regain the weight. As their weight increased, their leptin levels normalized.

  23. Thanks, Dr. K., for continuing to tie together the Quilt of Optimal Health! It's wonderful to see the background of how you tied it all together to come up with the Leptn Rx.

    Losing weight with HCG seemed like a miracle to me, but finding how to make my body really WORK again so I can LIVE LIFE in a wholely healthy way is an absolute God-send! YOU are here by His Divine plan for such a time as this … I'm sure of it!

    Again, THANK YOU, THANK YOU, THANK YOU!!!

  24. Speaking of clocks, Dr. k the clock on your blog comments is way off.

  25. Fantastic..! Dr. Kruse, this is one of the best you have ever written.

    I have a question about the deaf by birth people who are now hearing by the cochlear work that you have mentioned.

    Since they are well past 6 years in age, Do they learn accents if they learn 2 new languages? Is there any data on this?

    • @Resurg Interesting question. Based upon what I know about the neural correlates of language coding in the cortex and I think deaf people will never have the proper accent of their native tongue even after the cochlear implant is placed. I think however since this area of cortex was never coded for it it maybe possible if the implant corrected for it…….and I dont believe the current generations or the implant do this. I will ask my ENT friends about this.

  26. If I understand you correctly; in terms of reward theory, brain tumors in that area (dopamine receptors?) should cause obesity, and that isn't reported; while tumors in the hypothalamus tumors do cause obesity?

    • @Charlie Let me be crystal clear……if the reward tracts were or are the dominat cause of obesity there should be hundreds of cases of gliomas in this region of the brain that causes both obesity and cachexia………and there is no series in the literature that shows this. There are however thousands of cases of this with tumors of the hypothalamus. This is where the leptin receptor is and where the brain accounts for electrons from food that our mitochondria turn into energy (ATP). And this is why it is the dominant factor in obesity. What I am attempting to do is show you how the brain accounts for it so you can get to optimal. I think focusing in on macronutrients is a complete utter waste of time because humans account for calories based upon how their hormones set their epigenetic switiches in the hypothalamus. Most people dont understand it and they default to what they think makes sense. I dont. HAving been obese and knowing that calorie restriction is a loser option I began to think about obesity as a brain disorder and I used all the knowledge I have accumulated in neurosurgery to put this all together. It is meant as a starting point before you go primal 100%.

      Those signals are then neural wired to the reward tracts. Just look in this blog how prolactin has to answer to leptin and its binding and how dopamine plays a role in the inhibition of prolactin release. It certainly plays a role……..but it's no kingpin.

  27. wow thank Dr Kruse… this blog is awesome! All the timing stuff brings up a question… about getting labs. Would it be beneficial to get certain labs done at certain times of day? And what about labs that require fasting?

    • @SteveO it is……but that is when you are finishing off your optimal routine. When you begin there is generally a lot of fat on the bone so to speak. I do recommend doing all the testing first thing in the AM in the fasted state.

  28. I have been following the reset for 8 weeks, and find myself waking up after only 4-5 hours of sleep, I always used to sleep for 8 hours and had to wake by alarm clock. Is this a sign of LS?

  29. Thank you so much for this very detailed and understandable piece! Along with LisaAPB in that I'm hypothyroid and have sleep apnea, and too, was told I'd have sleep apnea regardless of weight because of my throat size (wondering if she and I have the same Dr…). I've been sleeping better since eating primal so much that I've stopped using the CPAP, although I am still quite overweight. This article has me determined to dig out the machine and start using as of tonight. You're a busy man and this was a lot of information – thank you again for your efforts to educate us all.

  30. dang it, I was afraid of that. That means I'll probably have to rely on the CPAP for proper sleep, even when I get slim. So the small throat caused sleep apnea, and the sleep apnea contributed to weight gain, thyroid disorder, and everything else that went kaput over the last decade.

  31. Jack,

    Thank you so much for this post. I may have not been able to completely follow every thought in it (I'm sure my eyes glazed over at least a couple of times) but I got the gist of it.

    Just FYI I started your leptin RX on the 10th of Oct. and have lost (as of the 25th) 10 pounds! I've been low carbing since January with no success (I actually gained about 10 pounds).

    Since I"m 64 and lost my "parts" about 10 years ago my hormone levels were pretty much flatlined. In June I "discovered" the Wiley Protocol and began that therapy in July. My sleep, attitude EVERYTHING has steadily improved since then.

    Your Rx seems to be the final piece of MY puzzle. So thank you for that.

    I do have to say, though, that choking down 50g of protein for breakfast is becoming more and more difficult. This morning I left 1/4 of a pork chop and about 1 egg behind. I. Could. Not. Eat. Another. Bite.

    But I CAN go all day without eating again until supper and then I don't need much.

    So now I'm off to read your posts on vitamin D (of COURSE my levels are LOW! I'm blonde, live in northern Wyoming and avoid the sun like the plague. But I have a bottle of 5,000 units/capsule I just picked up at Costco so maybe that will help. The 50,000 units per week prescribed by my Doc did nothing).

    Oh yeah, something strange is happening. I get a little hungry about sundown and HAVE to eat and then I HAVE to go to bed about 10:30. weird. ;-)

  32. @Joe S no waking up after 4-5 hours is a sign of a sleep/metabolic issue remaining. It means follow the Leptin RX protocol until that resolves. It will.

  33. @DrJack, thanks for the clarification. I am very unfortable with the reward theory; make sense that obesity is wired deeper the past.

    I came across your blog about 3 weeks ago. Been giving it a try. 6' 170 pounds. In 3 weeks have lost about 4-5 pounds. Removing alcohol, slighly better eating is helping. I think the light cycle — avoid TV/computer after 7 or 8, and switch the candles — is making the biggest difference for me, to be honest.

    I doubt that I am leptin resisant — have been this weight for about 20 years. My GF (5'7", 130 pounds) is trying something similar. It has not been working for her.

    I'm certainly sleeping better than I ever have before — up and at them at 6:30 AM. I just wish there was a bit more sun these days…

  34. Colleen Coble says:

    But we don't overeat, Doc. If you knew how little I ate and gained and gained you wouldn't say that. I personally don't know an obese person who eats the way people think they do. Carbs matter but not calories.

    • @Colleen who said anything about what you eat? You asked about calories……I know obese people dont eat 10000 calories a day. They cant. But they can still gain weight eating 1000……because calories matter to them and they cant tap their fat to burn.

  35. Colleen Coble says:

    I have been thinking about what you said. Maybe ALL calories are turned to fat when we are LR because the brain doesn't know what to do with them. So it's not that we can even cut calories t stop that from happening because the brain doesn't know how to apportion any of them properly. I can actually see that from personal experience.

  36. Colleen Coble says:

    Ah I see you basically said what I was surmising. I totally get it now. Thanks!

  37. How do nocturnal prolactin surges fit into the equation of resetting leptin sensitivity?

  38. Cú Chul says:

    avoid TV/computer after 7 or 8, and switch the candles –

    are candles alright for reading after 9?

  39. Disregard Q on prolactin, you explained in beautifully…

  40. What level of leanness can men expect to achieve once LS? Will LS get rid of those "last 10lbs", or does it require another level of metabolic functioning to get rid of love handles? Do epigenetics play a part in how lean we can become?

    • Charles you can get as lean as you want. All it takes to get it is to change how you think about leanness and diet. If you are reading this and living a paleo lifestyle you are closer than 99% who are home running on a treadmill with their personal trainers eating whole grains and taking statins.

  41. Thanks for the explanation for Leptin Rx. I have been managing type 2 diabetes for the past 10 years with a low carb diet. Now I have incorporated your recommmendations on sleep, exercise (at night) and avoiding pro-inflammatory substances such as grains and omega 6 oils. Believe it or not, but I lost even more weight and feel even better. However, my blood sugars still stay higher than I like, rarely dropping below 100, except temporarily after vigorous exercise. Do you have any additonal tips for type 2 diabetics? Are my receptors able to heal? Is my continued high blood sugars due to my beta cells in the pancreas burning out? My big concern right now is producing too much advanced glycation end products.

    • @bobP. T2D just need to extend the leptin rx reset longer because they have tremendous levels of inflammation and most have horrendous tissue and serum O6/3 ratios and are deficient in so many nutrients its not funny. But they can all be fixed if they have the patience to follow the leptin Rx then transition to a paleo/primal template. I have reengineered many this way and you can too. Its not rocket science……..it is brain surgery without a scalpel!

  42. "are candles alright for reading after 9?"

    No. But I have a red LED light that works great.

    There are, of course, other things to do after 9.

    • @charlie. You made me laugh because last winter i had a big stall and i thought it was night light inhibiting my hypothalamic thyroid axis. So i went out and used red LED site lights on my hat while i read in the dark and i used candles too. It turned out my vitamin dropped to 56 and i upped my K2 and D3 dose and withing 2 weeks i was back in business. And your implication about sex…..is quite true. Having more sex in the winter also helps a lot.

  43. @LisaAPB – just restating what Dr. K said about jaw abnormalities. My throat was smaller because of bad braces. The Dr. used headgear and pulled my teeth back when I was a kid and closed my airway. Fast forward 30 years and I have problems. I found a great dentist who is changing my bite and has opened my airway. Last spring it was so bad that I choked on vitamins and had to call 911. Shouldn't happen now as my airway is more open. I actually travel 6 hours each way to see this dentist. Few know about this or take it into account.

  44. Cú Chul says:

    who knew a medical blog could be this exciting?

  45. Dr Kruse: If you eat a large amount of carbs after dark it is spikes NPY, IL-6, TNF alpha, and raises sdLDL release at our liver.

    What is a large amount of carbs? veggies and starch carbs?

    If you eat the same amount of carbs-what you call a large amount- during the day, it won't generate a release of sdLDL? As one who has an extensive history of CAD in the family, minimizing small LDL is of importance. I am of normal weight, thyroid ok and my liver puts out tons of LDL particles, the size dependent upon the amount of carbs consumed. I do not know how this genetic programming can be altered. Your thoughts on all the foregoing?

  46. @steve honestly this is an awesome question. It totally depends on how your currently partition calories. If you are epigenetically handicapped to carbs the answer is none to maybe ten grams? A guess by me. But it is not a lot. If you are anthony colpo or carb sane you can eat up til you fill your liver will fill with glycogen and spill over into sdLDL. I bet Colpo has a better muscle reserve than carb sane though.

    Steve seriously now, context is total critical here. Most people on the leptin rx cant handle carbs well. So you really want to limit it. If you are on to finishing touches and involved with HIIT regularly you can jack it up…….but your better off doing it earlier in the day than later. Its too risky to block leptin from the in door. When i test people and see they can expand carbs without any problem i push them to IFing and hormone testing……..for body comp issues if they are what the patient is wanting.

  47. @steve,

    I would send you to Jimmy Moore's site where Dr Rosedale replied to Paul Jaminet's "safe starches" theory. The bottom line, there are no safe starches in the world of Dr Rosedale. One of the reasons is manufacturing sdLDL.

    http://livinlavidalowcarb.com/blog/more-safe-star

    Dr Rosedale's rebutal starts about a quarter of the page down…it you don't want to read other responses.

    You can alter your genes by how you think and what you put into your body. Dr K says it a lot. Change your thinking will change your genes.

  48. I have publically commented on Rosedale's response and I said on facebook it was rockstarish. I meant it too. I think Rosedale and I swim in the same pond, but it is a big pond……….we treat sick people. Paul sells books to young paleo/primal folks who are not looking for major overhauls generally. His diet in this context is a good piece of work. I have no qualms with Mr or Mrs Jaminet or their book. My public comments to Jimmy about his "safe starches blog" and cancer were specifically toward cancer patients. That got lost in how my comments were published and perceived. I am a big boy and can handle it. I apologized to Paul in a PM for sounding like a jack ass. I meant no harm to him or his book, i just thought his blog on cancer and carbs was bad. I consider him a a vital paleo tribe member. But at times we must disagree if we think something is wrong. Carbs and cancer is wrong based upon my readings. I wrote a damn blog on what to do with a new cancer diagnosis so my thoughts on this subject are public. You can search it on my page.

    The leptin Rx is for life changing maneuvers to get back to optimal. Once leptin is working a paleo template is perfect for maintenance of optimal. But optimal must always be worked upon……it is never attained completely…….why? See Rosedale's coments.

    I respect Ron a lot. He put his ideas in book and im giving mine away. I do it because one of my fellow MD buddies told me it was my duty to help people now and not wait for a book. I decided he was right. Plus my goal is to change medicine……my goal is not what other primal/paleo folks are into. I know whatnis broken and i must walk the walk and talk the talk. My first blog post was written from my heart…….Chasing Change.

  49. @kami look at my last blog on "teeth" and check out post 79. My old dental classmate Dr. John Sorrentino who opened his mind to the paleo message, has now petitioned the NIH to study paleo dentistry and malocculsions. This plays right into sleep apnea. I cant tell you how proud i am of John stepping up to the plate and push dentistry to look at the evolutionary record. Dr. Unger, is already a pretty famous dental anthropologist and has wrote books on the evolutionary changes of teeth in many animals. This step is another step to a tipping point for paleo living!

  50. @Lori. Regarding sleep and leptin and the cell cycle…….For evolution to work a cell first must adapt to its environment.  So the first thing a cell would see in an earth day is a period of day and night.  It also has to eat to make energy and it also has to control its own cellular division.  So in essence the circadian cycle has to "yoke" to the metabolic cycle and its growth cycle.  Evolution apparently agreed with that assessment because we now know it to be true.  When it is night time, the cell becomes more reduced chemically and electrically.  (A lower redox state like we saw in the mitochondrial series).  During a low redox time cells are usually recycling their components using autophagy. During the day while energy is being made to explore the environment the cell is more oxidized because of increased leakiness of the mitochondria.  Another interesting coupling occurs with the between the circadian cycle with the cell cycle.  They are linked via the PER 1 and PER 2 genes.  PER 2 directly effects the cell cycle in mitosis.  Mitosis is the phase in the cell that occurs just before cell division to generate an offspring.  The mammalian period 2 gene plays a key role in tumor growth in mice; mice with a mPER2 knockout show a significant increase in tumor development and a significant decrease in apoptosis (levee 19).  This is thought to be caused by mPER2 circadian deregulation of common tumor suppression and cell cycle regulation genes, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45α, as well as the transcription factor c-myc, which is directly controlled by circadian regulators through E box-mediated reactions.  This means that sleep is tied directly into to cell cycle functioning and directly into cell mediated immunity at some level. It appears that sleep directly effects the chronic diseases of aging and likely plays a role in cancer development.

  51. @kami. I wore braces too as a teenager. My upper jaw had to be expanded by splitting the bone and letting cartilage and scar tissue fill in.

  52. Doc,

    Thank you for this very detailed post and thank you more for repeating what you're after in your comment no. 68 above. You know you are making waves and there will be a tide, sooner or later, my gut tells me sooner. Just keep talking the talk and walking the walk. As you said elsewhere, truth is "true" rather than "right" or "wrong" and this always plays out in the end.

    As this is a Leptin Rx post, you have mentioned a ketogenic variant of it based on fat. Here's my take, does it sound sensible?

    Coconut oil by the spoonful in the morning and protein-rich "lunch-dinner" sometime in the early PM on days with hectic mornings.

    Things transposed on other days (protein-rich morning, coconut oil by the spoonful as "lunch-dinner" (easy morning typically implies hectic day for me).

    Just full-blown coconut oil from the car trunk"if all else fails" and the day is crazy or one is away from real food.

    …plus keping all other Leptin Rx protocol aspects (meal timing, no snacking, enough sleep)

    …plus Omega-3 supplementation & supplementation for cortisol reduction as you mentioned in your other posts.

  53. if i eat near bedtime, and especially if i have had refined sugar during the day- i wake up hot at night and have to peel of layers.

  54. @Brad Your question about Growth Hormone…….here is the more in depth answer with regards to cortisol and obesity and sleep apnea. Most people with SA are obese and have cortisol issues.

    CRH directly blocks secretion of Growth Hormone secretion as well. This means you get sarcopenia and osteopenia together! Low GH levels (IGF1) increase your body fat, decrease your lean muscle mass and increase your osteopenia to great degree. It also causes the cardiac muscle to fail and decreases the stroke volume. Sarcopenia is the result of low IGF1 or GH level, and is a harbinger of ensuing death, especially with respect to the heart. There is now excellent data to support the use of GH and testosterone for cardiac health in aging because of these effects.
High cortisol comes from stress. The causes of stress in humans are: psychological, traumatic, infectious, allergic, electromagnetic (EMF), xenobiotic and geopathic, as well as Leptin resistance and dysbiosis.

  55. Dr. K, thanks. I just forwarded the info to my Dentist.

  56. I just read an article by Dr. Oz in the Nov. AARP magazine about diabetes. He says the Roux-en-Y gastric bypass has been effective in reversing T2D in 80% of patients. He says the small intestine and stomach are endocrine organs, and the bypass somehow alters hormones that help regulate sugar response. What do you think of this?

  57. Thanks for a great response Dr.K and to Dexter for sending me to JMoore Dr.Rosedale response. Does raise several questions: the Japanese diet which is clearly high carb with much rice(3cups per day)seem to have much less diabetes,cancer(other than stomach) and CAD then we have. You would think they have on avg lots of small dense LDL; maybe it is the low level of fructose, Omega 6 and high level of Omega 3 that is protective and the small dense LDL are therefore not that big a deal.

    It might make for a great post to compare your ideas with Rosedale: i see overlap, but differences: sat fat vs. unsat fat; protein levels and mTor, as some areas.

    Interesting how such smart guys as both of you who read and understand the science can come to such different views.

    In my own case when i eat no starch i form little to no LDL per NMR which also shows me as very insulin sensitive. I also find that when i drop the starch a few pounds fall off my 5'6" frame, male, age 61. Thanks for all your work and thinking outside the box.

  58. Thank you for your post. Can your plan explain the dramatic success in reducing Hba1c levels in just a few weeks on a paleo diet? This is what Dr. Frassetto reported at her AHS11 lecture.

    • @ExceptionallyBrash: I think that talk does a good job but it should be intuitive…..the HbA1C levels rise because there is too much glucose in the blood for too long because of a failure of leptin signaling from fat, brain liver axis. If you fix the most rostral issue the rest of the biochemistry improves with time as signaling is restored. A HbA1C is in my view not a good enough test for diabetes but it what most use now. While it is not specific enough for DM because it is an indirect measure of insulin resistance at the liver level. I think RBC testing for Magnesium, serum insulin levels, serum leptin levels, rT3 levels and HS CRP levels with cytokine panels are way earlier markers of inflammation and better for diagnosis of diabetes. When most people are first diagnosed with T2D they have been IR for 4-6 yrs but fell under the current sensitivity and specificity of how we screen for diabetes. This is why I believe 150 million Americans have diabetes. Some people Like Dr Ron Rosedale think we all have it at some physiologic level. I'll leave that up to you all to decide who is more or less correct.

  59. I've re-read your Parts 1, 2, and 3 on Leptin and getting new insights. The part about breastfeeding struck me as I chose to breastfeed me own 2 children 19 years ago and they effortlessly maintain a naturally thin weight despite having a mother and father (who weren't breastfed)who've battled weight all their lives. I've attributed this to their being young…

    But I got a bottle – my mother was a newly diagnosed Type I diabetic (in 1968) still learning to control her insulin while she carried me. Now I wonder, what kind of inflammation tendencies did THAT set me up for?

    I've not been Dx'ed with either diabetes nor metabolic syndrome, but 70 lbs overweight, hypothyroid, with sleep apnea. Is it truly possible to clear what seems like a lifetime (and pre-lifetime) of inflammation up?

    • @Marie……..read my response to PAM and listen to the PODCAST I DID TODAY. I think it is possible but the research is very unclear on this. I was hoping Amgen synthetic trials would have went this direction but they ended their trials when it became clear they could not make money on synthetic leptin because of its extraordinary massive clinical effects and lack of control they had on them. I hope the future someone clones human leptin from a very fit person and we use that as the main drug. A synthetic hormone will never be optimal. Listen to Matt LaLonde's AHS talk to understand why that is a biologic and chemical fact. A synthetic drug never equals the true biologic response.

  60. You mentioned something I would be interested in expanding on and that was mention of the hypothalamus and age of 6 years old. I didn't fully get what occurs at that age but for me it was this age when the chubbies started and created a life long battle. Both my brother and sister are thin, not fair! What does this mean and is anything further involved in fixing it other than the reset? I have no other illnesses and rarely have to go to a Dr. I did have to have my gallbladder removed earlier this year but have no problems from that and can eat what I want including a good amount of fat.

    • @PamM Many people have asked this. If you go back and search my transgenerational paleo 3.0 blog part of the answer is there. The real reason I mention this a lot is because this is how the brain organizes data. Our personalities are usually set for a lifetime by this time, our ability to have an accent on our speech is set by then, and it appears our epigenetic switches are set by our leptin status then too. The reason for six……is simple. The brain fills empty cerebral cortex with specialized functions from the time we are born to the age of six. These circuits become used over and over again and the brain self organized circuits by how often they get used. The neurotransmitters play a huge role in how this happens and believe it or not sleep also codes for which memories are soft and which ones are hard. That means melatonin levels vary at night at the memory processing part of the brain called the hippocampus. The circuits that are associated with low melatonin signaling and low cortisol signaling tend not be be long term memories. Those associated with major input from excitement or say from a hot stove are coded for with different hormonal signaling and these memories are hard wired to long term memory. It appears the way we partition macronutrients and account for calories is hard wired in the leptin receptor by age six. It can still be remodeled but it is extremely hard to do because the biologic function of leptin is to prevent long term starvation and always provide a steady stream of electrons for our mitochondria to make energy. When the leptin receptor is "broken" by inflammation as it is in most cases of leptin resistance the only way to lose weight long term is to use the ability of neuroplasticity to occur to repair the damage. Most of that repair can only occur at sleep and the length of time it takes depends upon how much inflammatory damage was done and how you retrain or reexcerise the hypothalmic circuits to use alternative pathways to account for our energy status. We are evolved and adapt to use the leptin receptor……but we have the ability to use the older pathways that are present but not expressed epigenetically because they were never used much and their connections never strengthened by repetitive firing of neurotransmitters. Those alternative pathways are controlled by the circadian cycles in other sensory systems and people will respond to them when the leptin receptor is broken. To respond well we have to reteach the brain how to respond to them again. This is precisely how the leptin Rx is designed to work. In effect, the Rx are the dietary exercises to retrain our brain how to count electrons the old fashion way before we evolved the leptin receptor. We do know the leptin receptor is quite new in evolutionary times. Leptin however is quite old. But how it works now is a lot different than how mammals used to do it. I know its complicated but it is important to understand…….we can change leptin after 6 but you cant fight it using the leptin receptor that is broken and try to lose weight. That is the definition of a yo yo diet. Most diets are yo yo diets because they never address the leptin receptor that is broken and re teach the hypothalamus how to relearn old tricks. The research we need now it to find out can we always repair the receptor or are their some people who need synthetic leptin or have ther excess fat cells removed to fix this permanently. My belief today is we can repair them all if we give the receptor enough time, a lot of good sleep repair and keep inflammatory levels low as we employ the Leptin Rx rules. I think to prove this …….we can follow people with functional MRI testing and sleep studies to see how they do over time.

  61. On the Ketogenic Variant of the Leptin Reset.

    I have been KVLR for two months. It is not easy but it is possible and my bloodwork shows it is working well. I have one built in advantage, but that is all i have. My oven has a delay timer. So here is my method.

    before bed I prep my protein. for me that is 1.5 (avg) steak ( for agrument sake, could just as easily be salmon fresh or canned ) and allow that to sit in the fridge overnight. I set my oven along with my Lodge cast iron skillet to get to 400 deg F starting at 0530. When I wake at 0600 I place the steak in the oven. Iron my shirt, flip the steak. warm my coconut milk with unsweetened cocoa and Stevia and a big dollop of Coconut oil. Take the steak out. Sit and eat. Get dressed and get out the door by 7:15. Breakfast done.

    • @Jonathan……..Nice work. I usually put my meat in the crock pot the night before and cook it 8-10 so that it is ready about an hour before I leave for work. I use the meat by itself at times, in omelettes, or I add it to some bone broth I have constantly ready (from weekend of cooking grass fed bones) and make a morning soup to drink and drive with.

  62. Cú Chul says:

    where is today's podcast posted?

  63. @Owl…..some advice If Dr. Oz says anything run the other way. He is beholden to his corporate sponsors. Take a look at his site today on October 28th and he is trying to rebrand paleo to suit his own needs. Who in the hell thinks tofu, soy and grains are prehistoric but a moron?

    There is a tipping point coming and this ass clown is going to get hit with a major tsunami.

    Science waits for no one.

  64. @Melissa your email was cool about uncoupling proteins and their place in evolution. Beware of the science ahead.

    If electrons are allowed to flow down the chain uninterrupted but not coupled to ATP production this ends up in dissipating intracellular heat. (Remember the leptin posts about uncoupling proteins 1 and 3?) This allows mammalian cells to control their body temperature . Consider another opportunity it allowed us. If more of our "leaky holes" were partially sealed, this would allow us to make too much internal heat. This is not good adaptation if you evolved in say, in Africa? Sound like anyone you know yet?

    So uncoupling would be detrimental in that environment because you'd get heat stroke. Since we know that is where humans first evolved this could explain why we were able to adapt to different climates. We now know that this is true in tropical humans . The more free radicals that are made at rest causes more heat production. This is especially true on a diet high in carbohydrate (fruit) and protein that was common around the equator due to long growing seasons and exceptional vitamin D levels. Those foods generate more free radicals at the mitochondria due to increases electron flow. This would allow them to migrate north or south to colder climates. It appears to offset for the loss of vitamin D from the sun ApoE allele changes were naturally selected for to increase our D. Things were fine for many years with the APoE allele because the diet remained congruent with the natural selection. All hell broke loose in the last 120 yrs with the SAD and the emergence of AD.

    It also is clear diet effects mitochondrial stress levels as well and it is used as a signaling device in the cell…..to make new mitochondria or kill us via apoptosis or oncogenesis.

  65. @Steve……The Okinawins are always sited for longevity for the wrong reasons……It has zero to do with their diet. Their super centenarians have been studied extensively and all have a genetic defect that makes their first mitochondrial cytochrome less leaky to ROS so they age less and live longer. It has nothing to their macronutrients. Read this from my June 15, 2011 blog called dancing between purity and pollution. The Quote,

    " In 1998, Tanaka reported in The Lancet on the super-centenarians of Okinawa. He found that â…” of them had a single base change in subunit one of the respiratory chain where most leakiness occurs in humans. That one base change was responsible for their longevity. This was irrespective of their diets and life style. Many other authors have tried to link the Okinawans longevity to their lifestyle but it now appears that this blue zone occurs because that one base change makes their mitochondria less leaky at complex one."

    As for me and Rosedale……here is our major difference. He thinks high protein is bad because of the CRON data in every animal but humans and primates. Neither us or them CRON has shown anything convincing yet. It is being studied so we will see if he is right. I think high protein diets are fine if the cellular terroir is reduced and not oxidized. How does this happen. HS CRP is as close to zero as possible. Why do I think this? L-carnosine levels have correlated with telomere lengths to a major degree……where does carnosine come from? MEAT! I think the science of telomere biology is more vigorous than the CRON data. That is why we disagree.

    He hates Sat fat and says it harder to burn longer chain SFA. I call simple BS on that. There is not credible in vivo human data that shows it. Moreover, when when people eat a diet in high in SFA that has low PUFA levels and a low HS CRP they have optimal hormone status. Now Rosedale will point out that that pool of people is small……but the pool is not important when you consider all of the western world eats shit all day. Those who eat a paleo diet look like Art DeVany when they get to seventy. Again…..not an argument I see either of us winning because it wont be studied anytime soon……but people will do it his way and our way and see who body comp is better. Im pretty confident in this challenge.

    • @Peter In obesity we see increased leakiness of ROS at cytochrome one. This causes aging and neolithic disease generation and shortens our telomeres. When leptin is working well we can uncouple respiration by using UCP3 a lot and decrease leakiness. Aspirin is a mild uncoupler as well, and in my view this is the main reason one should consider its use instead of all the reasons stated in journals today. ( I dont use it) In calorie restriction, we have decreased leakiness as well due to low electron flow in the chains and this increases survival in mammals while living miserably. Some polyphenols like resveratrol and curcumin also decrease leakiness as one of their many beneficial effects. Another strategy for healthy longevity would be to increase our density of mitochondria so we had more capacity for ATP production. This is precisely what birds and bats do. Can humans do this? One way is to exercise……build muscle. Requires anabolic diet supporting testosterone and GH. See Art DeVany's lifestyle. (I love it too) So does PQQ increase our mitochondria? We don't know yet but some of the research being done on pyrroloquinoline quinone (PQQ) since 2003 aims to answer this question. This is why It is my top paleo supplement. Personally, I take 20 mgs of PQQ per day. I also use 500 mgs of trans resveratrol and a 1 gram tablet of curcumin daily. These doses change with light levels as the season change too. I want my mitochondria optimized.

  66. I laughed out loud at your Dr. Oz comment! I did see his "prehistoric diet". Yes, a complete joke. Vegetarian cavemen?

  67. Cú Chul says:

    great podcast, maybe even more informative than the more extended one with Jimmy Moore

    these podcasts are really helpful…

  68. Rachelle M says:

    Hi Dr. Kruse,

    Okay so on here I see theres a lot on hormones, and I posted on the HCG forums and they told me to ask you, but I'm 17, in the last 22 months I have lost 45% of my body fat or 122 pounds. (60 atkins, 62 hcg) I also haven't had a period in a year. My endocrinologist and ob/gyn said this is normal and not to worry about it, that it would resume on its own. What do you think? Should I get my hormones tested again? I went yesterday and my complete Lipid profile but what else would I need done?

  69. Thanks Dr. Kruse for your earlier response on Japanese longevity. Dr. Rosedale protein take is with regard to mTOR pathway which i think you will be covering.

    Maybe in the future you will be tying some of your thoughts in to heart disease. I have a long family history of heart disease-grandfather,father,brother all had coronary events, but we do not have hyperfamilialcholesterolemia at all and i am an ApoE 3/3.

    From NMR testing with CRP of .5 i think it may be due to underlying epigenetics and the liver producing lots of small LDL- a carb related phenomena. Through some of your writings and podcast(the one on get better wellness was good)i have experimented with diet,restricted or eliminated starch and small LDL per NMR goes real low to less than 90. Particle count is way high at 2200, nevertheless, and via experimentation only comes down if a statin is used(i know your view,but i am using it as testing) hsCRP falls on the statin to .3. No fructose and keeping Omega 6 as low as possible. Still the liver is putting out tons of particles and i bet this is the cause of the family history. Any thoughts on ability to correct the situation, or maybe it does not matter the amount of LDL particles, although they are far higher than LDL measurement would make you think- not 1:1 relationship. More fat in diet the higher the particles and HDL goes up but not as much as you might think. Anyway, to high an HDL may not be all that good i understand in some cases.

    thanks for all the input you provide all of us.

  70. Doc, your leptin prescription differs quite a bit from Byron Richards. Do people EVER regain leptin sensitivity following his protocol that allows grains?

    • @Colleen I dont think he wants them too……he sells supplements as his main income stream. Stay sick buy my shit schtick.

  71. That is just sickening! :(

  72. Its a gig that has worked for a long time for many. See Mercola etc.

  73. @Rachelle M I would not worry about it either. With a 122 lbs weight loss your hypothalamus is clearly re mapping and leptin is likely causing you a temporary hypothalamic amenorrhea reset. I would likely tell you to stop HCG completely because it will cause you long term issues with hypothalamic amenorrhea. Just eat primal and do the reset. You might be one of the people that has to do this for an extended period of time. I was one too because of my weight loss of 151 lbs. But eventually your hypothalamus re maps and you get to amazing places.

  74. I was jus diagnosed with MS 2 weeks ago and am leaning towards treating with diet, exercise, and supplements. Been reading so much on all this and it has my head sspinning. I've lost 127lbs doing crossfit style workouts, inconsistent paleo and no supplements execept for fish oil here and there. I'm not sure which direction to head in. I would love to hear your reccomendations please.

  75. I have been following a slightly modified version of the reset for a few weeks but this post made me question if the change I made is effective. I have been eating the large protein/fat breakfast when I wake up and then I have been eating lunch around 6 hours later but I have been skipping dinner as I am not hungry and it fits better with my schedule than skipping lunch. After reading about the timing with the light schedule, will eating the last meal in the afternoon when it is still light disrupt the reset? Thanks!

    • @Rachel You have to test it on yourself. For some people it does and other it does not. Let me give you an example. I have a patient who is extremely sensitive to the light cycles. Every time Sept to Nov he suffers a major plateau. So after two years of this he commented to me about this issue and he was really frustrated. I thought about it and told I thought I might have an answer. We did two tests a Vitamin D and an osteocalcin test. Both came back showing low Vitamin D and low K2 action. We massively change the dose of both and in 4 weeks he lost 15 lbs. He was amazed of the effect of the light on him. So now every June we draw his baseline labs and check him in Sept. He always falls but now we know what to do. I thought his stall was light dependent and the lack of light effects his gut flora……it stops making K2 and and this causes a some insulin resistance and his Blood glucose was higher than we expected. So he got a transient leaky gut and it had profound effects on his metabolism. I mentioned to him that 20% of T3 is found in the gut so when this happens it really can stall you out. This case is one I always remember because the response was so dramatic.

  76. if one increases vitamin d intake dramatically through supplements or use of a vitamin d lamp, what other nutrients should one supplement with? K2 only? k2 and magnesium?

  77. Dr K – this is the second time I have tried to use coconut oil and coconut milk. The previous time was 6 years ago. Each time I have a severe reaction. Eyes swell, throat swells, tongue get big I cannot close my mouth, my throat closes and my voice drops, hives etc. I take benadryl and it goes away. I really want to take advantage of coconut oil after reading about all the benefits. The first oil was from Tropical Traditions and the second jar was from Dr Mercola products.

    I am 67, female, 35 lbs overweight. I am taking all the supplements you recommend. What else to do except never use coconut oil.

  78. Cú Chulainn says:

    Dr. Kruse, is it possible that a subarachnoid hemorrhage could be related to Leptin Resistance?

  79. SK, what is your purpose for the coconut oil? If it's for the short to medium chain fatty acids, you'd do better substituting with palm kernel oil. Red palm oil is low in short to medium chain fatty acids. I use it because of it's superior nutritional profile (vitamin A and E, especially).

  80. @sk, those reactions can be simply be a Herxheimer reaction to dying Candida. Coconut oil is a potent anti-fungi and your symptoms point in that direction.

    @Dr. Kruse, do you have any opinions regarding Candida and the relation to your Leptin Rx? Many obese people tend to suffer from Candida overgrowth as well as Leptin resistance.

    • I think candida needs to be aggressively treated. But the diet has to be radically altered too because candida is hard to eradicate.

  81. Am I doomed? I had gastric bypass surgery in 2002. The MD on call dilated my anastomosis for stricture and OVER-dilated it. I am left with an extremely small gastric pouch that holds onto nothing. Another surgeon lengthened my limb to decrease my absorption. I am left to struggle with my weight (> 100lbs overweight)and deal with malabsorption. Should I even attempt the leptin reset?

  82. Thank you all that responded. I have a lot to read now and will respond again later. For background – was always thin until age 55, very active, loved to exercise. I am still active, but the weight has just been going up. I have been eating paleo per Dr Harris for 1 yr – no weight loss. I did however feel good. I have been leptin reset for 8 days. Stomach seems flatter and finally almost having a full night of sleep. I only eat grass fed beef, kerrygold butter and some pork. Not a vegetable fan, but once in awhile I eat sweet potatoes, white potatoes and turnip or collard greens.

    Have always been constipated with bloating. For these 8 reset days have not been bloated or constipated.

    One note that is strange – whenever I work hard, or do heavy lifting with wood etc my stomach becomes huge. Sometimes I look 9 months pregnant. After about 5 or 6 hours it goes down.

  83. Stepetic – I thought it would help the weight to go away faster.

  84. Dr K this is the 2nd blog where you've mentioned working out at colder temps (1st http://jackkruse.com/how-to-find-your-inner-maste… )

    I've always preferred WINTER and Winter Sports, snow skiing, snowboarding, snowshoeing…etc I yearn for the weather to drop below 40! I've actually seen my biggest weight loss from going primal btwn Dec – March of last year. I absolutely HATE Working out in summer – ugh (except in a very brisk swimming pool of 70degrees)! In the past I could never warm up when it was cold… but now while it maybe cold.. I'm loving it even more and I'm not cold… yes I still may be wearing the merino wool sweater, gloves hat and coat…but I'm not cold even though in the past I would have been. I'm guessing this preference for Winter "play" has been my body trying to drive me to optimal intuitively. BRING ON THE WINTER COLD! yet again… WOW!

  85. Hi SK. I'll let Dr Jack confirm this (this is is blog after all), but I believe he'd probably recommend the palm kernel oil over the red palm oil for weight loss, as it's the kernel oil that mimics coconut oils short to medium fatty acid profile.

    • @Stipetic I actually like both of these choices for coconut oil. I also like Lard and Ghee too……but neither gives the MCT load like the two you mentioned.

  86. I have read the articles and it does look like I have candida. I also read that if you have candida you also have Leaky Gut and you must take care of that first.

    Dr K I love reading everything you have written – sometimes 3 or 4 times plus all the comments. Wonderful site – thank you.

    Stipetic thanks for the Palm Kernel info and I can order that. On another site it also said that Pau d'Arco would help and I do have that in the house.

    I have no problems with wanting sugar, grains or eating between meals just cannot lose the weight that is around the middle.

  87. Dr K – shame on me. I just reread the Leaky Gut article and comments.

    There is the starting point I should be on. I do have L-Glutamine powder, and Aloe Vera Juice, I make bone broth from grass fed beef and I also make sauerkraut. If I add the palm kernel oil things might change.

  88. PanHypoPit says:

    Hello Dr. K~

    I posted the following on the hCG Diet Info forum. The Senior Members there said that I should try asking you here. Maybe you'll find this interesting. If you've already addressed it on your site, I'm sorry I didn't find it.

    I am panhypopituitary due to complete surgical removal of the pituitary and radiation therapy in 1985. I take all of the expected – and one unexpected – replacement hormones: Hydrocortisone; levothyroxine; Delatestryl; Genotropin. I have been stable on all of these since I started taking them – the first three in '85 and the latter in '05. I'm healthy and don't really have any (serious) medical issues. And I don't have a lot of weight to loose, around 20 – 25 pounds.

    Naturally my questions are: Are HCG injections too unsafe to add in with the rest of my regiment? Will it be ineffective because of the others? Are there adverse conditions and symptoms I need to watch out for? Do I need to adjust the dosage of any of the others while taking the hCG?

    I think I know the answers to the first 3 – Not unsafe; Should be effective; Nothing adverse more than for other people. And this is because I take "replacement" doses and my hormone levels are the same as for someone with an intact endocrine system. But the last one I don't know. A normal endocrine system might react appropriately to the presence of hCG, where mine is regulated only by how much I ingest or inject. I've searched all over that forum, yours, and most of the internet, looking for clues. The best I can find are those with variations of hypothyroidism who take their same replacement dose during hCG.

    I'll be asking my Endo at an appointment tomorrow. But I expect she will be unfamiliar with hCG or the protocol and will be predisposed to dismiss or even forbid it out-of-hand; if for no other reason than it's not FDA or AMA sanctioned. So I'm hoping to find a physician knowledgeable about hCG without that bias who might give their expert opinion. Any advise?

  89. Dr. Kruse-

    Do you have an optimal range for prolactin in males?

    I've actually been using Cabergoline to lower Prolactin it as I was having some issues with gynocomastia. In reading this blog I'm wondering if that's a very big mistake in relation to GH release during sleep.

    Also, do you have any opinions on using low dose Naltrexone therapy and Amitryptaline to break the inflammatory cycle in stubborn cases?

    Thanks

    • @Dru The levels depend upon the lab. And it also depends upon what we are looking for. FOr a normal level my lab uses this for males: 2 – 18 ng/mL. That being said I have seen gynecomastia in men in this range who have had head trauma, use of antipsychotics that block dopamine. Blockade of dopamine receptors in the tuberoinfundibular pathways results often in the elevation of prolactin and can cause gynecomastia. It can also cause galactorrhea (white discharge from the nipple), and in women amenorrhea. Bromocriptine has been used in the treatment of galactorrhea and amenorrhea due to hyperprolactinemia in neurosurgery for years.

      The most common cause of gynecomastia is use of anabolic steroids related to testosterone in body builders. This is a different cause than prolactin. It cause a conversion of the testosterone to DHT and E2 (estradiol) The estradiol drives the breast tissue and most men who do this use an aromatase inhibitor.

      I would suggest you check your E2 and PRL levels to see where you fall. If it is E2 you can use naturally methods to block the aromatase enzyme or go to arimadex with your doc.

  90. Prior to using Cabergoline my prolactin was 13.8 (4-15.2). It's now at .2.

    I think the gynocomastia was due to HCG usage as part of my HRT regimen. My E2 was all over the place. Whether or not prolactin was a contributor, I don't know.

    Since discontinuing HCG my E2 is now stabilized and normal (20) which has me wondering if I should still be suppressing prolactin.

    Also, any thoughts on the low dose Naltrexone therapy and Amitryptaline to help break the inflammatory cycle?

    Thanks

    • @Dru Dopamine has some major hypothalamic effects so if you dont need the cabergoline you might want to discuss that with the doc.

  91. " The significance of the prolactin surge (especially in older people) is made clear if you eat carbs within 4 hours of going to sleep. Prolactin release is yoked to the dark/light conditions in most mammals. It is also tied to NPY and to inflammatory cytokine signals in the brain. If you eat a large amount of carbs after dark it is spikes NPY, IL-6, TNF alpha, and raises sdLDL release at our liver."

    What about eating a meal without carbs right before bed? For example – a big bowl of bone broth, with a few eggs dropped in, along with some fermented cream?

    Thank you so much for your work.

    • @Ian its not just about the carbs. Their must be four hours between meal and sleep when leptin enters the brain at midnight to 2 PM. Timing is more important than macros!!!! don't forget this!

  92. Dr Kruse – 2 questions:

    1 I have a 10 yr old daughter who obviously has some leptin issues. She is maybe slightly overweight, has ADD (inattentive), tremendous difficulty falling asleep, and low energy. How should I implement the reset for her? (i'd really like to help her before puberty hits) How would it be different for a child her age from the standard rx?

    2. I had a roux-en-Y 9 years ago. The rest of my stomach and intestine are still present, just not accessible. No clue about the vagus (sp?) nerve. Should I bother trying the reset? Are there any changes I need to make to the basic protocol?

    Thanks!

    Janeen

  93. If you eat a meal that does not create an insulin spike (high fat, moderate protein, very low carb), is it still necessary to not eat at least 4-5 hours before sleeping? It seems that this would bypass the insulin spike that blocks leptin. Thanks!

  94. After a couple hours of reading your documents and blogs, I am impressed that there is solution to quite overwhelming issues I have recently been informed I have. (gallbladder removed two weeks ago @ 7% function, fatty liver, no ulcer, low D3, and extra 30 pounds I cannot shed) Stubborn and denial runs in the family.

    I am a bit discouraged that I would ever have opportunity for a leptin reset, since I have been a firefighter for 22 years – you know what kind of schedule we have: alarms at all hours of the day and night, inconsistent meals in the field, etc. I would have to retire to find normal or balance.

    I commonly have nightmares about work when I am off duty, and don't sleep soundly when I am on duty – anticipating calls.

    I am encouraged that I will find weight loss with intense workouts – joining Crossfit in three weeks, and with my new perspective on my low-fat eating habits. I'm hopeful that helps my sleeping patterns too.

    Thank you for your expertise, and for making the information understandble. I have a LOT of personal work ahead of me now, and some good direction to follow.

    • @Kimmie B If you're plan on eating a low fat diet as you suggest you will never sniff optimal. You need to fix your diet before you go to crossfit or you may pay a steep price. My life as a surgeon has some crazy hours so if I could make it fit anyone can if they want optimal bad enough. You must fit our biologic directives into your life to get optimal. If you think modern life needs to fit into evolutionary biology you will be like the rest of America…….in the dark with lots of artifical lights on and a big gut.

  95. I appreciate your reply.

    In anticipation of me refining my best direction to survive a healthy, fit lifestyle, with no excuses, would you agree that the Primal diet is perfect for me, and to reverse my fatty liver? My liver is priority – I would like to live past retirement.

    I recognize the importance of heavy lifting workouts, randomness exercizing, and the potential that the wrong foods will hinder my efforts. I could use some advise to fine-tune.

    I have started cooking egg whites with refined coconut oil instead of butter, just to give my liver a break right now, so should I begin eating healthy fats (butter and bacon) to help me drop fat? I am somewhat new at this, but I think I am getting the picture…

    Thank you again!

    • @KimmieB egg whites only? That is bad in a big way……you need the yolk to get the choline in the egg to get rid of the fat in your liver ironically.

  96. Ok, so starting from scratch.. from the research I have done, I also need vitamins to help my system repair itself, as well as a proper diet, sleep, etc. After the pain I have experienced in the last 3 months, I gave up eating and nearly even drinking water at one point- because of the pain in my belly that radiated into my back. I have lost 18 pounds from this within that time frame, and have been trying to eat low-fat to non-fat foods, based on doctor's recommendations, so I won't trigger pain any more. The non-fat diet during the last two weeks did not trigger pain. I am introducing fat back into my diet, and even vitamins hurt me – the radiated pain under my right shoulder blade, next to T8. I know that a non/low-fat diet is not practical for me when I start back with exercise.

    So far during my recovery from surgery, It has been my experience that baked chicken breast even hurts the stomach, at 3 oz. Oatmeal seems neutral, and I have only started that so I would not hurt the liver (bland) I have not eaten oatmeal for years until now, just to eat something. Ultimately, I prefer 3 eggs cooked in butter, but have been told that the fat content would hurt me physically – typically I experience a sharp pain around T8, right side, when I eat something that makes the liver unhappy. I am simply trying to survive without hurting. This process is hurting me every day.

    So I am being driven by the pain in my back, what I call "liver" pain, due to my fat liver. Foods trigger the pain, and I am starting a journal to keep track of what works and doesn't, so I will quit hurting. I figure if I hurt, my liver is not working right, Yes??

    I have little to NO support from my own GP, so my research is all me.. I am needing some relief, begging actually.

    Do you have any suggestions for my diet so that I can heal this liver and get back to being a productive, effective, fierce firefighter? I do not wish to hurt anymore!!!

    Thanks

    • @Kimmie B everything you need on what to eat is in in Robb Wolf's book called "The Paleo Solution" or Mark Sisson's "Primal Blueprint" . How you eat that food is laid out in my blog post called the Leptin Rx. That is where you need to start. You can buy the books wirelessly from Amazon or Barnes & Noble.

  97. Dr Kruse – perhaps you missed me? I am committed to Paleo eating, and have been eating and feeding my family this way for about a year. I have lost nearly 60 lbs on hcg this year. I have read your website, the hcg forum, and am stillworking my way through the MDA monster thread. I already imPlement most of your rules, but just need to know if I need to do anything different from or in addition to the standard protocol for myself (due to gastric bypass), and for my daughter (10 year old child)?

    Thanks!

    Janeen

    • @Janeen I did not forget you; I have not yet tackled bypass surgery. Bypass patients can rarely get to optimal unless they have access to synthetic leptin or more invasive surgery. Gastric bypass folks have special issues and they have to be handled totally individually. You need to speak with your doctor about this. The type of bypass is critical in figuring out what to do.

  98. @Sandy I just pulled this off PH. It points out precisely how fat and thin people differ. But what is not obvious to most people is how we can force the arcuate nucleus to under go neuroplastic change. The Leptin Rx and the Leptin Rx Postscript do just this. Their functional MRI's will and do change. A thought willl change your DNA.

    "These results are consistent with reports showing that high BMI is associated with decreased prefrontal activity at rest and after meal consumption and that obese subjects have an attenuated postprandial deactivation of the hypothalamus. These altered obesity-associated neural responses to food cues may contribute to overeating behavior, especially several hours after consumption of high-carbohydrate meals, a time when glucose often declines significantly below baseline levels."

    Thus, as the authors conclude:

    "These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity."

    They also speculate that:

    "Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods."

    One strategy to avoid drops in blood glucose levels is not to allow yourself to go hungry by consuming smaller but more frequent meals. The other is perhaps to chose low-glycemic index foods in order to prevent the 'crash-and-crave' drive that follows rapid changes in blood glucose levels.

    The study, certainly provides further evidence for important 'biological' differences between non-obese and obese people – while the former experience 'natural' appetite suppression with high-normal glucose levels, the latter do not experience such a suppression of appetite and will need to resort to conscious restraint – a far more difficult undertaking.

    http://www.drsharma.ca/obesityblood-glucose-level

    http://www.ncbi.nlm.nih.gov/pubmed/21926468

  99. Thanks, Dr Kruse. I don't think my doctor is going to be able to help me… I had a roux-en-Y. She is pretty open-minded, though, and I think she'll try. I just think this will be as new to her as it is to me.

  100. PS

    I understand I may not get to "optimal," but I'd like to think I can get to "improved."…

  101. I have postural orthostatic tachycardia. Can you offer any help for me? After receiving a swine flu shot I was horrible sick and got POTS. I've had it for 2 years. I'm stuck in fight or flight mode with a heart rate about 140-155. Thank you.

    • @Candace I would tell you to inquire about the Taub clinic in Birmingham, Ala. They maybe able to help retrain your sympathetic and parasympathetic systems if they are damaged using their science.

  102. Thank you much!

  103. Dr. Jack

    Can leptin reset be done with lacto vegetarian diet? I am insulin resistant with obesity, high BP and cholesterol. Trying hard to loose weight. TIA.

    • @Aliza I have several who are trying it now. But so far all of them have had long reset experiences. I think the protein and fat quality matters. If you have patience and time I think it will work.

  104. Hi Jack. Don't know how much you can help, but any feedback would be greatly appreciated. I underwent back surgery 10 years ago, which damaged the nerve(s) that serves my medial gastrocnemius and the lateral side of my left foot (both sensory and motor involvement). The medial "ball" of my gastrocnemius is completely underdeveloped. I wonder if you know what types of exercise would help reprogram my brain to use this muscle. I completed a Pubmed search on Merzenich, but can't find any "practical" information, if you know what I mean.

    What I've tried: Since the beginning of summer, I've been mainly barefoot (except for work) and noticed a slight improvement in sensation in my small toe, but nothing noticeable in my calf. Planning to start running barefoot later in the spring. I'm thinking the natural spreading of the toe in barefooting might send new feedback paths to the brain. Thanks in advance.

    • @Stipetic That sounds like an iatrogenic peroneal nerve palsy. That is not a good nerve to injure because it is one of those nerves in the body we have much difficulty getting to rewire. That all being said when there is sensory and motor involvement from surgery in the back region one could consider these two maneuvers…..stimulate the surface skin constantly with a TENS unit covering the peroneal distribution. You might also consider using a dorsal column spinal stimulator to be placed rostral (above) the injured site to stimulate the proximal peroneal nerve to rewire. I also think getting your progesterone, testosterone, DHEA and pregnenolone optimal before you do this to help stimulate rewiring. I think barefoot or vibrams is a great idea and I think anything that pronates your foot is ideal.

  105. Your work here, and free expertise, does not go unappreciated. Big thanks for the feedback, Jack.

    I think it's best if I look for a spinal guy I can work with. I eat paleo (been following the Leptin Rx for a while now, too) and take LEF complex with 5000 U vit D (with vit k2 and iodine). Can I optimize those hormones by only taking pregnenolone and DHEA supplementation?

  106. Dr. Kruse, if Growth Hormone helps reduce belly fat and osteopenia both, would it be prudent to take Growth Hormone while trying to lose weight while on the Leptin Reset?

    • @Kaleein those who have a documented GH deficiency before the reset do extremely well when it is added to the mix. The problem is few people get GH tested and even fewer can afford the GH monthly to use. It runs 800-1200 bucks a month not covered by insurance.

  107. Also, if low growth hormone increases cortisol, wouldn't taking it decrease cortisol and help us sleep better?

    • @Kaleein GH is very effected by sleep and cortisol. But GH can not be given in the USA for sleep problems because of federal law. It can only be given if one has a documented GH deficiency. If we could use GH for all the benefits it has I would love to use for all my obese patients who need to improve IR due to atrophic fast twitch muscle fibers and to improve the thickness of their skin and tighten it as they lose their weight and get loose skin. It has an amazing effect on skin, nails, hair, and body comp in those who use it correctly.

  108. Hi again Dr. Kruse, I'm 'staying the course' as you suggested, re T2D elevated blood-sugar readings (I'm just letting them do their own thing, within reason)….but I just read here that T2D's may well need to reset longer than usual. I've been at it for 6 weeks now and I'm concerned about deficiencies if I'm on next to no carbs = no veggies, etc. for much longer. I'm not clear on what supplements you recommend for extended resets…. suggestions? Thanks!

  109. @Julia,

    It seems that Dr. Kruse emphasizes the timing of food. I would also think the supps list given for the RX are still sufficient. Unless if you are feeling 'deficient' in some way, I'd look into it. Dr. Kruse always advocates for regular testing so that you're not 'flying in the dark'.

    Good luck!

  110. Hi Gladina, thanks for the response. I guess I was looking for a quick-supplements-list response but I'll suck it up and go deeper into this overwhelming information well of a site! ;) I've lost 12 pounds so far, gotten off ALL diabetes meds. Can't seem to get off the ace inhibitors (for hypertension)… yet… but still forging on and feeling good! SO great to be free of those former cravings and starvation headaches!

  111. I'm on my second week of the Leptin Reset. I have been struggling in many areas, but the one I want to touch on here is sleep. I am exhausted at 8pm after my final meal at 4pm. I fall immediately to sleep. I wake up 2 hours later, and again 3 hours after that, usually spending (without hunger) an hour or more trying to go back to sleep. This has been my reset pattern, and I'm tired!

    This morning when I woke up at 2am, I struggled with hunger, and gave in just after 3am. I fell asleep just after 4am, and woke up to write this post at 7am. Should I have fought with hunger longer and waited later? My usuall reset breakfast time has been 5am. Staying asleep from 2am to 5am has been very diffiult. This is the first morning I had to eat before 5am.

    I am not under a Drs. care, and I will be unable to do any testing. Is it safe to take DHEA or melatonin to see if I could improve my sleep patterns while on the reset?

    I have a very long history, and didn't want to introduce it here. I try to manage by studying the information you have provided, and applying what I understand to my own circumstances, but I'm uncertain if eating so early this morning was counterproductive in the reset process.

    • @Nina……its called a reset for a reason. It takes time to adapt. Sleep is yoked to metabolism. I have written about that too……in a blog. Search for it. And if you do not think sleep is a common problem just read the comment I post in the Leptin Rx comments #671. Stay the course and you will see it improve. You could add DHEA but I am a big believer for women it needs a labs test first to get the starting dose correct. You can have it drawn yourself too if you want. You do not need a doc to do it. I would suggest you join the monster thread at MDA and ask for residents for help with lab issues…….they are all experts now in many areas of the reset. They are great people and my helpers in changing the world of medicine.

  112. Thank you for your suggestion Dr Kruse. I have been dilegently studying all the posts over at MDA, even the section for new people, as well as all your blogs and comments here.

    I still feel a little overwhelmed by the science, abbreviated terms, and medical references that can go well beyond my comprehension at times, so I'm taking things slow. I do appreciate, however, the clear and concise outline that you have laid out in order for many people like myself to apply this technique when we see potential benefit.

    I'm a little scared too of the amount of food I can consume during each of my three meals. I ate my BAB this morning with almost 60 grams of protein + CO and a few vegetables. I was so full, yet I was still very ready to eat lunch!

    I'm trusting that I understand this program enough that I will see the postive results in the weeks and months ahead that I read so much about.

    Again, thank you for your response.

  113. Patty Cakes says:

    Dr. Kruse – Thank you for all that you do and sharing this wonderful information with the world (or all who will listen anyway). I wanted to share my story on the initial reaction my body has had to the Leptin Rx.

    I am a 53 yo female with Hashimotos. I started a very strict paleo eating plan on 1/1/12 with hope of losing some of the 15# of extra flab I've been carrying for a couple of years. About 10 days into that way of eating I discovered your blog and decided to go straight into the Leptin RX. Knowing I have a high rT3 (low FT3/rT3 ratio) I figured I was most likely leptin resistant. Also, I have slow adrenal function per a saliva test (very low in range at all four times).

    After 2-1/2 weeks I have lost a total of 9# and have more energy than I have had in years. Also my thyroid lab tests went beyond optimal and I had to reduce my dose of natural dessicated thyroid already! I was taking most of the supplements you have recommended and I am eating that darn BAB. I still have a little trouble getting it all down in the morning, w/in 30 min after waking, but it is getting easier and I am beginning to enjoy it. I sometimes don't need to eat lunch and other times it may be just a salad. Dinner is also lighter.

    Anyone who is willing to dive in and give it your best, I think you too will be surprised at how your body responds. I personally look forward to more increased health, energy, and getting more of my labs optimized.

    Thank you for changing my "World of Health."

  114. Hey Dr. Kruse. I have a question about magnesium. I haven't consistently taken it, but I would like to. Unfortunately, there have been some strange side effects for me. First, I have to take it before bed as it has the normal effect of making me incredibly tired. I usually start feeling it about 20 min after I take it (only 200mg). If I get to sleep within the next 30 min of it starting to work I sleep well through the night. If for some reason I don't get to sleep by then I can't get to sleep and start feeling very anxious and toss and turn all night with a lot of waking times. Why would it cause this? Second, if I take it for about 4-5 days in a row I actually GET restless leg syndrome… well I call it restless back syndrome because I feel it in my lower back where I just have to keep moving. It's weird and highly annoying and inhibits sleep for many many hours. Basically, I seem to have the opposite reaction that you describe with rls and low magnesium. Any thoughts on why?

    My other question is concerning the Leptin Reset. I am on the 5th day and things are going pretty well. I've always been a breakfast person so the BAB is easy enough. My problem is with sleep. I've always been a night person. I love being up at night. I understand this isn't optimal so I am trying to change this with your protocol and hoping this magically makes me a morning person. :) I also have the form of insomnia sometimes where I wake up many times in the night. I just roll over and go back to sleep, but I can tell if it happens for a few days I feel more tired the next day. I have no trouble getting to sleep normally though. Since starting the Leptin Rx I have been forcing myself to go to bed earlier and trying to minimize light as much as possible for about 3-4 hrs before I go to bed. I've started to feel tired earlier, but am now having a hard time getting to sleep. For example, last night I tried to go to sleep at 11:30pm.. I was tired, but I couldn't get to sleep until 12:30-1am.. then I woke up at 4:30am and couldn't get back to sleep until 6:30am. I finally forced myself to get up at 7:50am. I am still tired. This keeps happening since starting this. I keep waking up around 4 hrs after falling asleep and then fighting to get back to sleep for almost 2 hrs then forcing myself to get up early for me close to sunrise. What's going on?

    I was also wondering.. Should I try/force myself to get up around sunrise? I could sleep until 12 as I don't have to be up early for anything. SHould I sleep until I naturally wake up or do I NEED to get up early for the Leptin Rx to work correctly?

    Sorry for so many questions, but I didn't see these answered in your posts.

    • @Erica Mg is supposed to make you sleepy. It helps convert tryptophan to 5-HTP and on to melatonin in dark environment. Sleep is vital to optimal. There is no way around this. Neolithic life at night is not good for paleolithic genes. The way to tell is your DHEA level will be low and your IL-6 levels will be thru the roof when you have insomnia. This alone can cause adrenal fatigue and down regualte your T cell immunity. It also screws badly with your autonomic nervous system. All screw with your sleep. Turn the lights off at sunset. Get F. lux on all things electronic. You must adapt or live with sub optimal. Our biology is not designed for our neolithic life. These question are in many posts. All over the blog. Just search the sleep blogs I have done and the the Hormone 101 blog. I talk about sleep a lot.

  115. @Dr. Kruse: I know it's supposed to make me sleepy and that's fine. I was wondering why after taking it for 4-5 days in a row it makes me have RLS? You said that low Mg is a cause of RLS which I'd think taking Mg shouldn't give it to me.

    I've read all the sleep ones.. I will reread them today. I added F.lux and try to only use candle light if I can.. maybe I should start it earlier. It's just hard to do anything since sunset right now is at 5:40pm.

    My sleep question isn't about my previous insomnia. I'm hoping/assuming when I'm RS again that will be fixed. I was asking about my issues since starting the Leptin Reset. Since starting it I have trouble falling asleep when I never had that problem before. I wake up every night about 4 hrs into sleep and can't get back to sleep for almost 2 hrs.. which I never had that problem before as well. Is this normal on the Leptin Reset?

    As for my last questions about waking up at sunrise. I was wondering because in the protocol you say "eat BAB within 30 min of waking".. you obviously get up around sunrise, but it doesn't say "Get up at sunrise or earlier..". I was basically wondering.. Is it better to get up at sunrise even if I've only been able to sleep 6-6.5 hrs and will be tired? Or is it best to sleep a full 7.5-8 hrs even if it makes me get up at 9am or later? What's more important for the reset.. sleeping enough hours or getting up at sunrise?

    Sorry, I think I just wasn't clear enough in my previous post.

    • @Erica I dont think its the Mag causing it. RLS is a sleep disorder. You likely have a sleep issue and you need a sleep study done. Mag helps RLS it does not cause it. Sleep apnea causes most RLS. On a reset your supposed to have an adjustment period……that is why we call it a reset. I say you should sleep the full amount of time and then wake up. Sleep is more important.

  116. @Jack: Thank you. I am going to try tonight to make it darker earlier and see if that helps me get to sleep earlier. As far as I know I don't have sleep apnea. I've never had RLS before trying Mg and I never have it unless I take it 4-5 days in a row. It's weird I know. I'm going to try to take epsom salt baths before bed and see if maybe it's how I'm receiving it somehow that's causing the issue.

    • @Erica if you have trouble sleeping and you have RLS my bet is you have a formal sleep diagnosis. YOu need to see a sleep pulmonologist to check it out. Sleep apnea can kill you by cause a slow insidious R heart failure and lung disease.

  117. @Jack: I can only understand so much of the science that you write.. I try my best. You may have explained this and I didn't understand ,but is there a way to cure sleep apnea through nutrition or lifestyle of some kind?

    I ask because I have no insurance or any money. I imagine a Sleep Pulmonologist is a specialty dr. of some kind and I would have no way to go to one.

    Before Leptin Reset my waking in the night was sometimes, but not always. I also never gasp that I know of and no one has said I did who has slept with me. I know I snore sometimes, but not always. I am overweight, but have lost some and am still losing. (I'm almost 5'3" June:176 lbs my heaviest Today:152 lbs) That's the "criteria" I fit for sleep apnea that I've found on WebMd.

    Maybe I do have it, but I would think this isn't something that is incurable. Am I wrong? Is it something that's forever?

    • @Erica there is not data that says you can but there is also no data saying you cant. We know that sleep apnea is often tied to obesity. So eating will help it immensely. There are patients with SA that are not obese. They are a minority but I believe their problem is a mismatch of chronobiology. I have several patients who have all but eliminated their apnea with a ketogenic version of the paleo diet.

  118. @Jack: Interesting. The only thing that makes me think not SA is that one-legged standing fixes my waking in the middle of sleep issue. Not sure if you read Seth Roberts Blog, but he found it helps you sleep through the night. I thought it was strange, but decided to try it when I had more than one night of bad sleep. It works every time. He doesn't seem to know why it does and I def have no idea, but it works. :) Well I guess for now I will continue on the Leptin Reset and hopefully that fixes things and I don't have SA. I think I will do some one-legged standing tonight and see if it helps my new sleep issue from the Leptin Reset. Thank you for your advice and whenever I do have some money I will make sure to get checked for SA among the many other tests I would love to get.

  119. Dr Kruse:

    Since we are essentially switching to using the alternate light/distension pathway in the leptin reset, do you think the standard damaged/desensitized receptor pathway eventually repairs/re-sensitizes itself over time of disuse as one is using the alternate pathway? I know the typical dieted down/formally obese person's receptors are totally screwed up and the fat thermostat is still set on obese which is why as soon as thy let go of the manual diet pressure on the broken thermostat spring, they regain the weight. I realized you are now relying on the secondary/alternate thermostat which should work. I was just curious what the chances of this fixing/resetting the main thermostat are to lower set-point. From my research, the set-point can easily be raised, but not lowered. But that seems to be genetic since some people can eat a totally crappy diet and remain thin..they remain LS regardless and their thermostat doesn't rise as they overeat.

    • @BenG In the last ten years we in the neurosciences now know that the brain is a lot more plastic than we believed. In fact it is so plastic that it can rewire just by making small changes in the environment. I am actually getting very close to updating the Leptin Rx with a new factor called Factor X after doing a bio hack this year that has shown major benefits that are additive to the Leptin Rx. And BenG the new factor can absolutely lower your leptin level. There is a ton of data out about it but its not directed at how I use it clinically today. The work I did shows it works very well.

  120. Dear Dr. Kruse;

    I posted a question, but I forgot where I posted it…my bad LOL, so now I don't know if you answered me? Should I just re-post it?

  121. Dan in Utah says:

    You note that DHEA levels correspond very well with high IL-6 levels (98% correlation). Would this mean LOW DHEA correlates to a HIGH IL-6?

    Do you use the age and sex correlated cut-offs for DHEA or do you set an arbitrary level?

    Could you elucidate us on the how IL-6 and DHEA are linked biochemically?

    Thanks for taking the time to respond to all our comments!

    • @Dan Yes the relationship is reciprocal in warm adapted humans but not in cold adapted ones. I use it to assess autophagic efficiency. This tells me how bad their metabolism is and then I know their chemical clocks are really off. If you do not sleep you are not well. This is the clinical reason why. It is also why the young have great DHEA levels and those past 25 years today have horrible DHEA levels. Dan I could……and will at Paleo Fx. That is where the theory meets the practice. My clinical practice is all about bio hacks.

  122. Dr. Kruse:

    I take low dose Naltrexone before bed 4.5 mg, I also just stared growth hormone shots before bed and I take 100 mg Pogesterone before bed. Will any of those meds interfere w/ the re-set diet? I have Hashimoto's, so I'm also on T3-only time release 100 mcg in the morning and when I need to I also take Adderall for my ADHD. I have major LR, I'm 4'5 tall and 145 pounds, but 2 years ago I weighed 250 pounds. I also have IR, my fasting blood sugar is 105 and sometimes higher. My temps run low around 97.6 or so. Thanks, Lisa

  123. Dr. Kruse;

    Sorry there is a typo in my previous statement, I'm 5 foot and 4 inches tall, not 4'5, sorry!

    Lisa~

  124. Menopause! On BHRT pellets, thyroid compounded t3/t4. Still have many signs of post-menopause (at 54, I am 3 yrs into it: hair/skin/nails/digestion). Have looked , but don't see much about leptin reset and menopausal issues. I can believe that it works, and will use for HCG P3, but would love to hear more about post-menopause improvements. Thank you .

  125. Thanks. Just FYI – I understand re; pellets and I tried everything else – these have actually been much better for me. And again, glad to have found you!

  126. Dr. Kruse, is there a reason u answered Randy but not me? Naltrexone works on brain chemicals, so I want to know if it will interfere with leptin RX? I’m doing the leptin RX and it’s working and I stopped the naltrexone until hearing ur opinion but want to take it again if it won’t mess up the RX?

  127. I just read ur info on hair loss. Which I have at my part line on the top of my head and was on propecia for less than a month, but anyway my t3 only time release 100 mcg is causing me to have high SHBG, so is this something I should worry about??? The 125 mcg of Synthroid I used to take caused major hair loss, since being on t3 only now I only loose a tiny amount of hair daily in the shower verses a handful daily. But the high SHBG leaves less free hormones and I read ur info on longevity etc… So now I’m worried???

  128. I just bought ur cook book!

  129. Dr. Kruse, I do not see how that answers any of my questions! Naltrexone works on the endorphins in the brain, so will taking it interfere with the leptin reset???
    My doctor suggested taking it to help lower my Hashimotos antibodies, but I don’t have to take it! And do I need to do anything about my high SHBG, which is caused because I’m on T3 only? I have Hashimotos so my temps already run low 97.5 and I can’t take the cold at all, so no way will I do that, the reset is working great without doing that, I just want to know if I can start taking my low dose Naltrexone again or not? And I want to know if high SHBG is anything to be concerned about?

    • @Lisa it wont. But Hashimotos is not solved with LDN. It is spackle for a broken quarter panel. Your SHBG is die to your poor body comp. Changing your thinking and habits will lowly change it. You can take cold you just do not want to try it. And since you believe that I doubt I can help you. Good Luck and keep us updated how your plan goes.

  130. Dr. Kruse, If I understand correctly spiking insulin levels blunt leptin not allowing it to bind properly to receptors? I’m a T1D and I am currently taking high doses of NPH(long acting spiking insulin) in the evening to counteract really high AM bloodsugars, which has been effective, but will that impede the work I’m doing on the Leptin RX? I have also noticed these nighttime spikes are somewhat disruptive to my sleep.

    • @Cara no it wont but it can disrupt your sleep. After CT 7 is released you might realize why that is not a good thing. Sleep is vital to a diabetic.

  131. claudia rowe says:

    PROGRESS TO DATE:

    Week 7 Leptin Re-Set
    Weight Loss: nil
    Weight Gain: 3kg
    Medical Conditions: MS, lupus, DB2, colliac, Hashimotos.

    Hi Dr Kruse. Week 7 and progressing nicely. The tremor in my neck, which was skating close to disabling, is now almost non-existent. This morning I woke feeling full of beans instead of the usual keto-flu, and can even feel my muscles working.

    By that I mean, for the first time in years I feel that my muscles are propelling me down the footpath rather than me dragging my body towards an end point.

    Thank you again for your help. I find myself zeaously extolling your genius to manymany frightened people on several continents.

  132. Dr. Kruse:
    Poor body comp??? Over a year ago I was 250 pounds, today I only weigh 143 pounds, my target weight is 135 pounds. That’s less than 10 pounds!!! I’m doing the RX, because I wanted to end my sugar cravings and it has! I’ve always ate low carb and is how I lost all the weight (over 100 pounds!), but I ate late at night and I snacked, so I was always hungry. Not eating 4-5 hours before bed and only eating 3 meals a day, with a BAB has totally cut down my appetite and gotten rid of all my cravings for sugar! So why do I need to drench myself in cold water? For what reason exactly??? Because the RX has already worked and I’m only 8 pounds away from my goal, and I don’t think I have poor body comp! I’ve had a lot of plastic surgery after losing all that weight and I actually look pretty hot! Mini face lift, tummy tuck, breast implants, etc…, so my body comp looks good! But my Hashimoto’s antibodies are high and so my doctor told me that taking low dose Naltrexone would help with that, but from what you’re telling me my doctor is wrong, ok I believe you. But is it worth taking for anything else, because the low dose Naltrxone web site sure seems impressive, makes it sound like it’s the cure all!!! And my SHBG is high and my doctor said it was because I’m on T3 only, 100 mcg time release, and I’ve even read on-line that T3 only will cause high SHBG??? My question was will low dose naltrexone interfere with the RX and you said “no it won’t”, so I’m going to start taking it again, unless for some reason you don’t think I should or need to??? The RX is working great, so I didn’t want to ruin things with the naltrexone and so I stopped taking it until I could hear back from you! So now let me make sure that I understand you about the SHBG, you’re telling me that my high SHBG is due to the fact that I have poor body comp??? And it has nothing to do with me taking T3 only??? And what the heck is a broken quarter panel??? Sorry I guess I missed that day in medical school! I figure you got this Leptin RX thing down pretty good, since it worked right away for me, but now I need a little more help with these few questions, so help me please! Oh and one more thing, I’m 43 years old and I just stared growth hormone shots, any opinion about that and what’s the best time of the day to take them? I also have fibrocystic breasts and before my UFE I had uterine fibroids, so maybe there’s some estrogen dominance going on I’m guessing, my new doctor also has me taking 100 mcg of progesterone at night before bed, any thoughts? Give me your thoughts on all this PLEASE!!! I feel like your short answers are because I’m asking dumb questions???

  133. I will gladly pay you for your time, but when I go to the media page to book a consult with you it says:

    Not Found

    Sorry, but you are looking for something that isn’t here.

  134. claudia rowe says:

    UPDATE TO WEEK 7 PROGRESS:

    Hi Dr Kruse. Just gotmy 3 monthly blood tests back and my leptin levels have gone from 97 to 135?????? The highest they’ve ever been.

    Normal range hereis 15-50.

    I’ve been doing the Leptin RX for 7 weeks without a second off plan, following the principles exactly. IS this part of fixing leptin resistance or am I doing something I shouldn’t be/not doing something I should.

    Any assistance would be greatly appreciated.

  135. What? Not ready for what, to take clients or what r u talking about??? And are you going to answer my questions or not and if not then tell me so I can move on. Your short answers are so frustrating! And you assume everyone has poor body comp, my belly is flat as a board! To look at me I look like I weigh 125 pounds and i am 5 foot 4 and 1/2 inches tall, even though I really way 143 i look thinner and firm, i wear a 26 jeans same as a size 5-6! So my high SHBG is not due to poor body comp!

  136. Dr Kruse: Ok doc I read some stuff on paleohacks and now I think I get it. I didn’t realize how important you think it is to cold adapt at home, so yes I will do it! But I hate the cold, so it better work lol! I know ur busy so is there a way I can pay to consult with u one on one? And can I ask your “opinion” PLEASE….which time of day works best to take growth hormone shots? Before bed or upon waking up….when? I’m taking it b4 bed . Also if i’m taking t3 only should I worry about high SHBG and talk to a doctor or not worry about it and just cold adapt? And what is a broken quarter panel? PLEASE REPLY!

  137. I attached my pic (w/ my daughter), so you can see my body comp and this isn’t even a recent one, I’ve lost about 10 pounds since this pic was taken!

  138. I like your theory very much, but I do not understand one special point. You have stated, that the autophagy is not fully activated in leptin resistant persons, as their GH levels do not peak that high as they should.

    But how can the growth hormone be an activator of autophagy? I have never seen any publications on this. Rather GH stimulates IGF-1 and IGF-1 is an activator of the Tor pathway, which down-regulates autophagy.

    • @Hodzic I think your mixed up……when autophagy is its most efficient we release GH at its highest levels…….this occurs in humans in Stage three and four sleep…….modern lifestyle does not let most humans enter that stage long enough. That is the problem……..the way to measure the efficiency is the DHEA level. That tells you how good, bad or ugly sleep/metabolic efficiency is with a cheap blood test. Every patient i have seen with a bad DHEA level had a bad sleep study

  139. Jennifer Johnson says:

    @Rachelle M and DR K – just wondering if you ever did start TOM again. I started Hcg last July and haven’t had a period since. Now my doctor is sending me for a Pituitary MRI. And I’m thinking, is it just the hcg? Did it break my hormones forever? I hate having unneccessary expensive tests if it’s just because i took hcg.

  140. Tracey Romanillos says:

    Hello,

    I am 43 and I am Leptin Restistant, I recently found out from blood work by my doctor, she told me that I am a good candidate to try something new that she is working on getting to help with Leptin Resistance, I am very high, looks like I’m starving all the time. She put a lot of emphasis on this with my last blood work and visit with her. I also have inflamatory issues that my doctor can see in my bloodwork so she put me on Limbrel and she prescribed me to take fish oil 4,000 and d vitamin 5,000 per day in addition to adding iron slow release and metformin at night to lower the insulin beause I am borderline diabetic, my tryglyceride is high all the time too. She also prescribed me to take niacin at night before bed. She is trying to get my levels in check but I just wanted to let you know what I’m taking also so you know and if you have any thoughts you’d like to share on this would be greatly appreciated. I don’t know my weight right now because I don’t want to, it discourages me and it isn’t my main reason for getting healthy, I check by how my clothes fit and my problem is all around my stomach since I’ve had children. I know if I feel like something is happening I will eventually check my weight and keep track but for years now that hasn’t been the case and excerise hasn’t made a difference either. Oh yeah, is it ok to walk on the treadmill for 30 to 40 minutes a day while I’m on the Paleo? I am going to try the Paleo diet and see what happens, I have done the protein diet in the past and I don’t have a problem with eating a lot of protein, although the morning 1st thing will be tough since I’ve not been eating breakfast now or at least a big one for a while. We are told to eat several small meals a day and from what I read that is not correct. So I’m now retraining myself to think different and frankly it is not that hard for me, I think it makes perfect sense. I have to tell you that my doctor is the first one to start my thinking process on this Leptin issue, but then I decided to do my own research which kept me up late last night reading a bunch of questions and answers from yourself and I was so captivated that I couldn’t stop reading. I learned so much during the early morning hours and now I am sending you this message in hopes that I will get a reply from you personally. I have another question though, my daughter is 12 going on 13, she is a vegitarian basically since she was born, she can’t eat meat and honestly I couldn’t eat meat or poultry while I was pregnant with her, so I had a difficult time with that pregnancy and it explains why I couldn’t breastfeed because this is precisely when I most probably got my Leptin issues, before that pregnancy I didn’t have the cravings and I was thinner. I gained about 80 pounds with that pregnancy also. My 2nd child was different, I had no problems and she eats a lot of meat, she is a protein machine. I gained no extra weight during that pregnancy but I’ve been having trouble getting the 1st born pregnancy weight off for 12 years now. My question is about my daughter, she is an artist of course, her sleep patterns are weird, she is up at night and busy drawing and she plays piano and strings instruments. She won’t eat meat, trust me there is no way, she is so different from other children her age and she is tired during the day in school and I know she doesn’t have any energy. She is not over weight but I worry about her and I was wondering how could I implement this Paleo diet into her life, what could she eat in the morning 30 min. upon waking that would make the required 50g of protein? She is a carb eater and I give her b12 pills every other day to help with the protein defficiency. She eats some peanut butter and nuts, what can I do to help her in the future? I am trying to help her before she becomes an adult. I’ll keep you posted on my new Paleo lifestyle change for myself and my husband will be doing it, he had a stint put in a couple years ago when he had a heart attack, he’s 54 and his doctor/my doctor keeps track of his health with bloodwork every 6 months and he is taking a lot of supplements and some prescriptions to help with cholesterol and high blood pressure etc. I think that he would benefit very much from this and he loves meat so here we go. He also is hungry all the time. I believe his Leptin was also very high when his blood was tested. Thanks so much and I look forward to your reply. You are a genius and I am excited to find you.

  141. Jimmy Pagan says:

    Hi Jack. I wake up at 4am Monday thru Friday to commute to work from Pa to NY. In your start guide you recommend eating first meal within 30 min of waking up. Should I eat my first meal so early and space my next two meals evenly throughout the day and how important is it to eat within 30 min of waking up. Thank you for your time.

    • @Jimmy it is pretty important……eat as you drive if you must but the earlier it is to rising is important.

  142. Andre van Staveren says:

    Dr Kruse,

    How can the brain know how much fat to burn? Does your blog imply that the brain uses setpoints for energy homeostatis? If so, is there a protocol to reset the setpoints?

  143. Andre van Staveren says:

    Dr Kruse,

    I know. Leptin is the signal/feedback. But the brain sends the UCP-3′s for the uncoupling. So the amount of leptin is critical, but where is the treshold? In the receptors, the number of receptors or in the brain. (tinking cybernetics now).

    • @andre everyone thresholds are set by their cellular surroundings. That is the premise of Levee one in the Quilt. It makes epigenetics penultimate in my theory. And if you are reading the Brain Gut series I think you should begin to see why now.

  144. Andre van Staveren says:

    Thanks; I’ll read them again.

  145. Looks like some researchers are waking up to the importance of the timing of when we eat.

    Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet Look partway down his 5 July posting to see his description of this just published study on mice;

    When fed a high-fat diet, C57BL/6J mice develop inflammatory symptoms and ultimately, metabolic disease. What Du, et al. wanted to know if circadian metabolic oscillations influence the response of mice to a HFD. They used a restricted feeding regimen, which has shown to reset some circadian rhythms. They found that, although eating the same calories overall, mice eating all of the calories from the HFD during an 8-hour window do not developed the symptoms exhibited by mice eating a HFD ad libitum (see figure). In other words, eating the same unhealthy diet at the same level of calories, but restricting it to an 8-hour window, practically abolishes all the deleterious effects***. This effects were mediated by preventing the abnormalities in the circadian rhythm induced by high-fat feeding.

    In other words, as I have read somewhere here, “WHEN you eat, is as important as WHAT you eat”

    How many doctors ever tell their patients that?

    The Pubmed abstract for this finishes with;

    We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

    A nonpharmacological strategy – what are the chances of the pharma funded med establishment endorsing this?

    In his other July posting, he talks about how the digestion of fats, especially long chain ones, causes an inflammatory response. And how the body needs time (hours, not days) to get over it and return to normal. In other words, leave 4-5 hours between meals for your body to recover, and don;t snack – precisely the opposite of what every dietician is telling us!

    • @Paul N patients in my clinic have heard that line out of my mouth for 7 yrs now. I personally think it was my greatest discovery in healing myself.

  146. HI Jack,

    Thanks for the fast reply!

    It amazes me that the only mention of “meal timing” from conventional dieticians, is to have snacks between meals! Though some do at least say to always eat breakfast.

    I have to say, that following your meal timing, and non snacking, rules has helped me tremendously. Combined with giving up wheat, I no longer want to snack, and most finger/snack foods contain – wheat!

    Of course, my grandmothers advice was along the same lines, three meals, no snacking, and dinner at 6pm!

    When you are not carb-craving it is easy to do this

    She also had the greatest answer to a kid’s request for a snack..

    me “I’m hungry”
    Her “then have an apple”
    me “i’m not that hungry” !

  147. They can see their monopoly is threatened, and, like so many professional groups, are more interested in preserving their position/monopoly than in ensuring the truthfulness, and usefulness, of their message.

    The heart and Stroke assn, diabetes assn, cancer, etc all seem more interested in perpetuating themselves, and their diseases, than curing them…

    Hippocrates would not approve…

  148. Here is another study showing why protein is the fuel in the leptin Rx: http://www.nutritionandmetabolism.com/content/1/1/5

  149. Here is another study showing why protein is the fuel in the leptin Rx: http://www.nutritionandmetabolism.com/content/1/1/5

Trackbacks

  1. [...] Acute stimulation with pro-inflammatory cytokines results in increased serum levels of leptin, whereas, chronic stimulation by IL-1, IL-6, or TNFα leads to reduced levels of serum leptin.  So chronic stimulation is seen in clinical scenario’s with chronic high cortisol levels and very low leptin levels…….and this causes anorexia where the signaling becomes uncoupled between leptin and ghrelin…Ironically, this is the precise mechanism that bariatric surgery affords the morbidly obese because the stomach is cut free of the vagus nerve.  This is why obese T2D can stop their medications the day after a standard gastric bypass proceedure even after years of diabetes.  The reason they do not lose weight like and anorexic is because the brain immediately begins to to rewire to the peripheral signals in the gut that the surgeon created.  Within a year most weight loss stop because the vagus nerve rewires at the hypothalamic level to the leptin receptor.  This is the same reason a vagal nerve stimulator does not work long term for obesity treatment.  In AN the brain can not rewire because of the defect in BDNF and neurogeneisis.  In the morbidly obese this system remains intact and viable.  The brain can immediately figure a way around the bypass by defaulting to the in utero system I discussed in this blog. [...]

  2. [...] Article 2 - The basics on the LR (leptin reset) [...]

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