My Leptin Prescription

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I have been asked by many to put a short post out about how I reverse Leptin resistance in my own clinic for my patients. After reading all of the comments left here, at MDA, and on Jimmy Moore’s forum, I decided that it was a good idea.

1. First make sure you really are Leptin resistant (LR) to begin with.

The easiest way to do this if you are heavy is to look in the mirror. If you’re overweight you definitely are Leptin resistant. If you still have a large appetite and crave carbohydrates, especially at night, these are also signs that you are likely Leptin resistant. If you are fit or in decent shape and not sure based upon the above symptoms, I would tell you to go get a blood test and check your reverse T3. It will be elevated. I also recommend simultaneously checking a salivary cortisol level. With LR, you will always see higher cortisol levels later in the day.

2. To regain Leptin Sensitivity (LS) follow a strict Epi-Paleolithic diet.

To see an outline of a strict Epi-Paleolithic diet, read Brain Gut 6: Epi-Paleo Rx. The type of fuel you eat is important initially in eliminating the foods that cause Leptin receptors to become nonfunctional.

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WHY YOU NEED TO THINK FOR YOURSELF

READERS SUMMARY: 1. Why you should be disgusted with our policy on diabetes. 2. How is one to survive the situation. 3. What can you do to avoid this situation and to thrive?   I read an article this morning in my local Sunday paper that stopped me dead in my tracks and caused me to write this. Majid Ezzati is the chairman of global health at Imperial College of London and his study was just published in The Lancet just last night. The study was based using data from 150 published national studies that followed adults over 25 years in 199 countries. The study used modeling to estimate the numbers for 92 other countries. I am not a fan of this type of science but I have to say, I believe they under-called the problem in a big way. The modeling did not take into account the three youngest generations world wide. More importantly, It failed to include the youngest three generations obesity crisis in the biggest problem country. That country is the USA.   When I was on Jimmy Moore’s podcast this May, I estimated that the numbers in the USA for type two diabetes were north of […]

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Why Sleep and Leptin are Yoked?

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To begin to understand how sleep interacts with metabolism, we need to understand a bit about neuroanatomy. In sleep, the cerebral cortex is in a state of cortical synchronization. In wakefulness, several subcortical regions of the brain stimulate the cortex to remove this synchronization. When we undergo slow wave Non REM sleep (drowsiness) there are a small group of neurons in the hypothalamus called VLPO neurons that are GABAergic (inhibitory) and they fire on the subcortical areas that are stimulating the cortex. In doing so, these VLPO neurons bring about cortical synchronization. After sleep begins, NREM sleep gives way to REM sleep. During REM sleep there is a coordination of cross talk between the grey matter brainstem nuclei while cortical synchronization is maintained. This is quite complex coordination of events that occurs in the brain while we sleep. A common disease of dis-coordination of sleep is Narcolepsy. In other words, the tracts that normally control the stages of sleep occur out of sequence and cause people to fall asleep and lose muscle control in wakefulness. Narcolepsy occurs because we lose a specific set of neurons in the hypothalamus that effects this coordination of signals. These neurons are called the hypocretin neurons (HC). These neurons are found in the ventral lateral hypothalamus in a small area that also control appetite and feeding. These neurons also effect loops that effect feeding. There is no set point. When we lose HC neurons we set up the neurochemistry that becomes resistant obesity. The dopamine tracts are the direct targets of the HC neurons. We don’t see obesity as a common phenotype when we see tumors of surgical ablation of these dopamine outflow tracts. This is the main reason many do not believe there is a set point for obesity. The hypocretin neurons sit scattered through many MSH cells (also involved in obesity). The HC neurons make two peptides called (hypocretin 1 and 2)HCrT1 and HCrT2. In the literature, these peptide hormones are also known as the orexins so you do not get confused. These peptides are remarkably similar to gut incretin hormones that help tell the brain what type of foods are present in the gut. Another remarkable trait of the hypocretin neurons is that in the human brain there is only 50,000 total HC neurons in an organ with over one trillion cells. And they appear to be very new in mammalian phylogeny. It appears mammals handle sleep and energy metabolism very differently than the rest of the living. The small amount of HC neurons, however, project widely all over the brain. We now know that the hypocretin neurons control the stability of wakefulness or our arousal. It appears they may also control energy metabolism via leptin function.

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WHY DO WE SLEEP?

READERS SUMMARY: 1. Why do we sleep? 2. Does sleep control metabolism and cell growth? 3. Do all living things sleep? How long is too long or too little? 4. What are the stages of sleep? 5. Can sleep help prevent degenerative aging diseases and cancer? 6. Is sleep the primordial condition or did it evolve as we did?   Why do we sleep?  Well, most sleep researchers are losing sleep trying to find that out as well right now!  It appears to be an elusive target.  What we do know , is that when you don’t sleep a lot of bad things happen.  Disease propagation is one and psychosis and eventual death are others.  Most people don’t realize that lack of sleep is deadly for humans, but it clearly is.  Sleep appears to most to be a restorative physiologic process.  That is what they say now;  I am not so sure about this as yet.  If sleep is restorative, as they say, what are its targets?  We have no idea what the targets really are as of now.  What we do know about sleep is that it is incredibly important biologically because every animal has biologic sleep requirements.  It seems evolution has strongly naturally selected sleep […]

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WHY DIETARY BIOCHEMISTRY?

READERS SUMMARY 1. Quick overview of carbohydrate metabolism 2. Quick overview of fat metabolism 3. Quick over view of protein metabolism 4. Are all exercises created equal? 5. What exercises optimize us for health and longevity?   The process of how food is turned into ATP is called cellular respiration.  Foods are made from carbohydrates, proteins, and fats. This a quick overview of dietary biochemistry to show how our foods and mitochondria have to interact.  Carbs have four stages of metabolism that allow them to be transformed into CO2, H2O, and ATP.  Stage one is called glycolysis.  It has either 10 or 11 steps.  10 if they occur in the cytoplasm, or 11 if they occur in the mitochondria.  It begins with glucose of glycogen and ends with pyruvate under anaerobic conditions.  It only allows for 2 ATP to be made form glucose and three if glycogen was the source.  It also liberated 2 hydrogens in the form of NADH.  Stage two carb metabolism has no name but it allows formation of Acetyl CoA from pyruvate.  This occurs in the mitochondrial matrix without oxygen, but is an aerobic process.  No ATP is made but two Hydrogen atoms (H) are released to make 2 NADH.  Stage three of […]

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A Leaky Life?

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Okay, now that we established that mitochondria leakiness determines our lifespan, what can we say about disease generation? Does leakiness determine disease progression? Well, it appears it does. We know that lower life forms like yeast accumulate mitochondrial mutations one hundred thousand times more frequently than in their nuclear DNA. Most of those occur in the control region of the mitochondrial DNA (mtDNA). The new theory of mitochondrial aging is that leakiness of free radicals at the first cytochrome also helps weed out those mitochondrial mutations as we age. Why? Mitochondria that are sluggish to the signal to divide because of the mutation would be taken out by apoptosis very quickly. Moreover, if the mitochondria were in perfect order, it would divide immediately and through clonal expansion lay waste to its inefficient brethren. This is intracellular natural selection at work. So the more mutations in the mtDNA coding region the more leakiness occurs. That leakiness is the signal to the nuclear DNA to make new mitochondria. This pathway is called the retrograde response. This is how a defective mitochondria signals the nucleus that something is amiss. In theories past, we always believed it was the nuclear DNA that set the tempo for such decisions but now we know that power rests with the mitochondria. This retrograde pathway is found in yeast all the way up to humans phylogenetically.

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Dancing Between Purity and Pollution

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Mitochondria can allow life or kill us. Mitochondrial DNA has only 37 genes. From those 37 genes comes just 13 proteins. Those 13 proteins code for the electron chain transport complexes. The remainder of the genes code for tRNA. Mitochondria also cant grow outside the cell. They require the 30,000 genes in the nucleus to make up another 1500 proteins for them to function. Mitochondrial DNA and nuclear DNA have to have precise lock and key fit to generate energy production. If not, the cell eliminates itself by apoptosis (levee 19) fast. If It works well, this combination is naturally selected for future cell division to generate energy. Aging is quantified by how “leaky” our mitochondria are to free radicals at complex ones in electron chain transport. Their own DNA is adjacent to the first complex in electron chain transport. So the more leakage, the more damage is done to its DNA and energy production will fall. Moreover, that is the signal to make more mitochondria or undergo cell suicide! This first complex (NADH) is by far the most leaky to free radicals of all the complexes. This paradox of fate caused evolution to select for 10-20 copies of mitochondrial DNA in each cell to sustain energy production of an organ in question. So mitochondria can breathe life into us and end it based upon how many good mitochondria we have in a tissue.

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What Powers Life and Death?

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Mitochondria are the parts of our cells that generate energy. We now know that the leptin hormone controls how the brain maintains its pulse on energy generation. Today, we are going to go over how the powerhouses in our body generate that energy and why it is critical to us in disease and in health.

Mitochondria were stolen by animal cells from a primitive bacteria. The reason? It allowed simple plant and yeast cells to no longer be a prisoner to the low energy generation of fermentation and photosynthesis for energy production. If you don’t have enough energy in the cell you can’t make future plans to make complex tissues like a brain unless you provide the energy for future cell divisions and evolutionary growth. So animal cells seem to have symbiotically absorbed a Rickettsia like bacteria to harness the energy it could make. This bacteria generated a lot of energy by using the sun’s light to generate sugar from carbon dioxide and water. That process is called photosynthesis. Photosynthesis allowed for a much more efficient energy production than fermentation. This chemical process was further refined by evolution and natural selection in the mitochondria to form a chemo-osmotic gradient on the inner surface of the mitochondria to generate massive amounts of power compared to simple bacteria. This evolutionary change has allowed evolution to proceed to very complex structures like the human brain.

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Why Does Heart Disease Really Occur?

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Let me begin by saying, I think western medicine is ideal for acute diseases. I know this is a dogmatic statement to lead with, but I believe this to be true. And those diseases are the ones that shortened our lifespans most in the first half of the 20th century. Most people I talk with always want to know why I think medicine has missed the boat with respect to chronic diseases? I have thought long and hard about this one and I think I have arrived at my reason. Healthcare, up until the 1940′s, was done anecdotally and by empiric observation. In the 1940′s, the government saw some statistics that showed close to 40% of the deaths in the US were caused by heart disease or stroke. It also appeared that the numbers were accelerating and not slowing down. The real reason they became interested is that no one knew why this was happening. So they decided to study this problem with a long term observational population study that began in 1948. That study was the Framingham Heart study. The bible has the book of Genesis, and physics has Einstein’s theory of relativity and Framingham is medicine’s raison d’etre.

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How to Change Your Doctor and Your Life

Readers Summary 1. Why humans can change their DNA with a thought. 2. Are we mismatched? 3. Motivated by Paleo Hack thread. 4. Why convention healthcare fails us. 5. What we can do together to change that. CHASING CHANGE Humans evolved the attributes of a large brain, the ability to speak, and formed an intricate social networks that can use many aspects of technology. Our biggest attribute is the ability to think. This allows us to radically change the environment that we are ideally adapted to. It has allowed us to dominate all habitats and create havoc in most of them as well. The real human miracle of our mind is not that we can see the world as it is…but that we can see it as it is not and then change it. If we think and act incorrectly, we can quickly recalibrate and overcome it. Conversely, we seem to be a prisoner to our paleo-cortex (older, less evolved brain) and resist change even when we know it must occur. Many times we will subjugate the best interests of our survival to suit our emotional needs or desire. The real paradox of humanity is that often our reasons for […]

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Hormones 101: Clinical thoughts revealed

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Readers Summary Why I use highly sensitive C-reactive protein (CRP) and Vitamin D as biomarker proxies. After Leptin, Cortisol is the next most important domino to fall. Hormone Cascade explained in a paragraph. Unintended consequences of hypercortisolism destroy health. Initial HS CRP signals the genesis of underlying hormonal disruption (First sign Leptin is toast). Now that we have laid some foundation about Leptin at the “30 foot research level” (I know, I made your head hurt at times), let’s zoom out now and look at how this affects the hormones that dictate the things patients see and feel and sense about their bodies. I want to now give you some perspective as to WHY this matters We have established that as one gets fat, Leptin levels rise. Once they get high enough (around a Body Mass Index (BMI) of 20-24), Tumor Necrosis Factor (TNF) rises in several tissues. This also causes a rise of NF kappa beta and IL-6 in the brain.  TNF quickly destroys normal hepatic homeostasis, which sets the stage for fatty liver disease and type two diabetes over time. This rise in TNF also biochemically changes Leptin receptor signaling and changes its quantum properties by changing its […]

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Why is Oprah Still Obese? Leptin Part 3

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Now, we know definitely that Leptin controls all energy production by regulating all the hormones in the body. But, do you wonder what happens when that regulation goes awry in the muscles? Well, here is some information about one part of how Leptin works to keep us fit when your body is sensitive to it.

When Leptin was discovered in 1994, no one really had a clue as to its many functions. One function that was particularly murky was how the brain controlled peripheral energy utilization and optimized it. It is awfully hard to realize that the hypothalamus (size of a pea) can control the need for fuel of 20 trillion cells in the human body. Well in the last few years, scientists found out about uncoupling proteins (UCP). So far five have been discovered in mammals. The one we will discuss today is UCP3.

This protein, UCP3, allows Leptin to work inside of peripheral cells like the muscle cell. For UCP3 to work optimally, it requires optimal functioning of Leptin and thyroid hormone simultaneously. In muscle cells, UCP3 is the dominant UCP in humans. So it is vital to maximizing efficiency in exercise and energy use. What UCP3 allows the muscle to do, is to shift out of regular oxidative energy production done at the mitochondria and making energy in the form of ATP, and into making pure heat without generating ATP. This biochemical action decreases ROS (levee 3) at the mitochondrial level, decreasing cellular stress. And therefore the energy is dissipated mostly as heat. Another protein, UCP1, is dedicated to doing this same action when it is activated 100% of the time.

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Leptin Part Deux: Liver

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Many people are under the assumption that the thyroid is the real key to metabolism. I can’t tell you how many meetings I have been to and heard this nonsense. It happened today while I was speaking to a dietician and nutritionist in a hospital. It’s just not correct. The liver is the engine of our body’s Ferrari! The thyroid is best described as the gas pedal for the engine and leptin is the electronic chip that controls the entire process. So we need to discuss some biochemistry now. Rub your head a few times before we start to increase your blood flow!

When humans eat a meal about 60% of the calories wind up in the liver to deliver energy to tissues between meals to sustain normal energy production. Another hormone, Glucagon, mediates this release of fuel. The remainder of the energy (40%) is sent packing to the peripheral tissues and the muscles where insulin allows the energy to enter the cells. If those cells are leptin sensitive they use all 40% of the calories with nothing left over. If they are leptin resistant the excess calories go directly back to the liver to be placed into fat storage (or stuck inside the liver cell) in fat cells because of the high insulin levels. The more fat that gets deposited, the higher leptin levels go over time. If the fat gets stuck in the liver it causes a large immune reaction driving up more inflammatory chemicals. When it gets to a critical level (different body fat levels for all people) the fat begins to make the bad stuff. (IL6 and TNF alpha)

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Leptin: Chapter One

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

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My Epiphany For Your Future

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Everyone knows the capability of what we can do in surgical care has dramatically increased in the last decade. I used to have to make large incisions to repair the spine or the brain back to health. Now most of my incisions are less than an inch long and some are the size of pencil eraser. Over the last decade my abilities has changed dramatically because of technology. Surgeries that once took many hours now take less than an hour. And most are not done in the hospital any longer. Moreover, the recovery times have also shrunk from months to weeks. Some of the operations for a fractured vertebrae (spine) due to osteoporosis used to be brutal for patient and surgeon. Now I can repair them through the skin using a needle half the size of a number 2 pencil in less than ten minutes. To show you just how far we have come in surgery let me share with you a short video to give you an idea of what is actually possible now in 2011.

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Living An Optimized Life: The Dr. Jack Kruse Story

Greetings, my name is Jack Kruse. I am a neurosurgeon and I would like to share some ideas with you. These ideas are very important to me and I have been considering them for quite awhile now. Why do I want to share it this way, you may ask? Well, the “WHY” is the actual answer to that question! Let me explain. As doctors, our medical training in school and residency really focuses in on HOW we do things and WHAT we trying to help you with. We spend very little time explaining WHY we do what we do for patients. This may seem trivial to you now, but it is critical to understanding why patients often get frustrated with us physicians. For five years I have been fortunate in being able to meet, examine and operate on people of all types. In that time I noticed something was radically changing before my eyes in those patients. At first, I thought it was a quirk finding — a coincidence, if you will — but then one particular disease kept popping up in all age groups and in all sexes. It also became increasingly common in all types of cases I […]

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