Ron Rosedale, MD
13 January 2008
Ron Rosedale, M.D., is an internationally renowned expert in nutritional and metabolic medicine and a specialist in the biology of aging. Dr. Rosedale has helped thousands suffering from so-called incurable diseases regain their health. He is the author of the recent books, The Rosedale Diet, and Insulin and its Metabolic Effects. He is currently chief medical officer at Advanced Metabolic Laboratories in collaboration with the University of Colorado and lives in Denver, CO.
To successfully treat any disease, one must know what disease to treat. Treating only a symptom of the disease will leave the underlying disease unchecked and possibly worse. For example, we evolved the "runny" nose to help us clean out upper respiratory infections. So taking a decongestant to eradicate the symptom of a "runny" nose is actually counterproductive for the underlying disease.
Symptoms are the way that evolution has taught us to deal with disease. What are normally called diseases - heart disease, diabetes, obesity, arthritis, osteoporosis, autoimmune diseases, arthritis and cancer - are all chronic symptoms of aging. The biology of aging is teaching us that aging itself, though not curable, is treatable.
If you are not treating aging, you are treating a symptom, and you do not know if the treatment will be worse than the "disease" that you are trying to treat. It matters very little if 10 studies show that a drug improves risk for heart disease if it also increases risk for cancer or other diseases of aging. What you really need to know is its effect on mortality rate and, therefore, aging.
Much of what we know about longevity is derived from studies of humans and animals who have broken the age barrier for their species. The longest lived flies may survive only a few days, mice a couple of years, and dogs for one or two decades, depending on their size. Humans currently have the potential to live at least 120 years, but few actually do. The average life expectancy today is around 80 years, which is impressive but nowhere near our full potential.
Growing in ranks, yet still few in number, are the exceptional group of people who live to be 100 years old and more. Scattered throughout the world, these centenarians are providing scientists with a living laboratory from which they can unravel the secrets of longevity. If we can figure out why these folks managed to live so long, we can use this information to extend the life span for everyone.
It would be easy to dismiss longevity merely as a function of luck, that is, simply a matter of winning the genetic lottery, but we know that this isn't exactly true. That's a good thing, for it means that we may be able to control our own destiny. We have been controlling the longevity destiny of laboratory animals for decades.
Laboratory animals put on calorie-restricted, nutritionally complete diets provide an equally rich source of information on longevity. Since the 1930s, dozens of species have been fed calorie-restricted diets, including microscopic tiny worms, assorted rodents, and more recently, rhesus monkeys - fellow primates that are closely related to humans. These animals virtually always live longer than normal - 30 to 300 percent. Assuming a "normal" human lifespan of 80 years, this would be the equivalent of a human living to be 104 to 240 years old.
Of Mice and Men
At first glance, human centenarians would appear to have very little in common with calorie-restricted animals. After all, humans can eat what they want when they want, and many centenarians did just that. There is no evidence that centenarians followed a particular diet or even had particularly healthy life styles. Some centenarians smoked, some did not; some exercised regularly, some did not; and some were careful eaters, and some ate whatever they felt like.
Despite the obvious differences, there are some striking similarities between caloric-restricted laboratory animals and free-living centenarians. Centenarians and calorie-restricted animals share a particular bio-metabolic profile that distinguishes them from their peers who die younger and sicker. We now know the common denominators that are found in almost all living beings - whether they are worms, mice, monkeys or humans - that defy the odds and live beyond their expected life span. In nearly every study, the longest lived animals share the following traits:
- Low fasting insulin levels
- Reduction in fasting glucose
- Lower body temperature
- Low percentage of body (visceral) fat
- Reduced thyroid levels
- Low triglycerides
- Low fasting leptin levels (Leptin is so new that it has only recently been measured in centenarians, but it has been measured in calorie-restricted animals. Since leptin correlates with and even controls these other biomarkers in humans, this is also probably true in centenarians.)
Why are these factors shared among long-lived individuals in all species? A very important finding of the various genome projects, including the human genome project, is just how similar our genes are to virtually all other animal species above bacteria. All of the important basic metabolic processes necessary for life are shared among nearly all species. That means that we have virtually the same genes as the ones that allow laboratory animals to live to twice their usual age or more.
The major differences among species, and particularly within a species, stem from which genes are allowed to be read, or "expressed," rather than from what genes are present. We have virtually all of the genes that a worm has, but we don't slither along the ground because we keep those worm genes under wraps, or "silenced." Many genes, however, can be turned on or off, and this mostly depends on their nutritional environment. Perhaps the most important of these genes regulate aging.
Virtually the same genes appear to regulate the factors that determine longevity in nearly all forms of life, including humans. Caloric-restricted animals may not have been born with the profile of longevity, but their diet enabled them to express the genes that recreate it. In other words, eating less has reprogrammed their genes to extend their lives.
You too can create a favorable genetic environment that is likely to not only extend your life, but help to keep you "disease"-free for as long as possible. You can actually make your body decades younger and turn back the clock to a time when you weren't weighed down with all that extra fat, or when you didn't have diabetes or heart disease...and you don't have to live in a cage on a caloric-restricted diet to do so.
Why We Age
Before we talk about how we age and the mechanisms that appear to control it, we should talk first about why we age. It takes energy to make babies - or in this case, new cells - lots of it. Throughout life's history, energy has been very precious and very limited. Just as you budget your bank account, every living thing must decide how its energy currency is to be spent.
The primary choice is between maintenance and repair, on one hand, or reproduction on the other. This is similar to the process of caring for your car. You must decide whether it is cheaper to keep repairing your car or whether it would be more economical to buy a new one. Furthermore, it makes no sense to waste energy making babies (new cells) when there's not enough energy available to be successful. You can't buy that new car if you can't pay for it.
Instead, it seems that virtually all living forms can "switch gears," actually switch genes, in times of food shortage. They can direct energy away from reproduction and toward mechanisms that will allow them to "hunker down" for the long haul and wait to reproduce at a future, more nutritionally opportune time.
In other words, nature will allow you to live longer to accomplish its primary directive of reproduction. It does this by turning on maintenance and repair genes. When you are in maintenance and repair mode, the body's "fix-it shop" is fully staffed and ready to go. Calorie-restricted animals and centenarians have measurably higher levels of key chemicals that extend life and promote repair, including antioxidants such as glutathione, catalase and SOD. These chemicals protect cells against damage inflicted by free radicals, which can accelerate aging and promote disease.
Calorie-restricted animals and centarians also have higher levels of very important proteins called heat shock proteins, which protect other vital proteins from being damaged and misshapen. Proteins communicate with other cells by "touch," much the same the way a blind person uses Braille. When a protein is misshapen, it will give bad instructions to other cells, which will interfere with the normal functioning of the body. The up-regulation of heat shock proteins is vital for a long, healthy life.
DNA repair is also bolstered. This all happens when you restrict calories in animals, and has been shown convincingly over 70 years of research to greatly extend their lifespan. Thus, there is a powerful link between energy stores, cell reproduction and longevity. One could guess that there must be signals that indicate energy stores and regulate the genetic expression of longevity genes.
One would be guessing right.
Our health and life depend on how accurately instructions are conveyed to our cells, so that they can act in harmony. It is the communication among the individual cells that determines our health and our life. The communication is carried out by hormones. Arguably therefore, the most important molecules in your body, the ones that ultimately decide your health and life, are hormones.
Many would say that genes and chromosomes are the most important molecules. Once you are born, however, your genes pretty much just sit there. Hormones tell them what to do, whether to act or not. Certainly, the most important message that our cells receive is how and what to do with energy, for metabolism and therefore life cannot take place without that. The two most important hormones that deliver messages about energy, and therefore control metabolism and aging, are insulin and leptin.
Two Critical Hormones
Metabolism can roughly be defined as the chemistry that turns food into life. Insulin and leptin, therefore, are critical to health and disease. Insulin and leptin work together to control the quality of metabolism (and, to a significant extent, the rate of metabolism).
Insulin works mostly at the individual cell level, telling the vast majority of cells whether to burn or store fat or sugar and whether to utilize that energy for maintenance and repair or reproduction. This is extremely important, because, at the individual cell level, turning on maintenance and repair equates to increased longevity. Turning up cellular reproduction, on the other hand, increases the risk of cancer.
Genetic studies in simple organisms have convincingly shown the link between energy stores, reproduction and aging to be at least partially mediated by insulin (which in simple organisms also functions as growth hormone) When insulin signals are kept low, indicating scarce energy availability, whether or not, in fact, energy is scarce, lifespan can be greatly extended.
Levels of insulin are largely determined by glucose (and amino acid from protein) levels. In many people with diabetes, insulin levels are also determined by how much insulin they are taking. Many have been told that what they eat does not matter as long as they take enough insulin to cover it.
This couldn't be further from the truth. Consider two people with equivalent blood sugar levels but who are taking different amounts of insulin. The person taking higher amounts of insulin will likely age faster and accumulate the "diseases" associated with aging, such as heart disease, obesity, and even diabetes itself. Yes, that person's diabetes will get worse. Why? Because most cases of type 2 diabetes are caused by overexposure to insulin.
Just as you become unable to smell the odor in a smelly room after having been there awhile, your cells become unable to "smell" the essential messages from insulin (and leptin) after they have been exposed to high levels of these hormones. Your body responds to this inadequate signalling either by producing higher levels of insulin and leptin or by requiring more to get the message across, contributing to a vicious cycle.
In short, low insulin is very healthy and good for you as long as its message is being heard. Most treatments for type 2 insulin-resistant diabetes, however, involve drugs that raise insulin or utilize injections of insulin itself. Treatment of type I diabetes also generally requires excessive quantities of insulin.
The tragic result is that conventional medical treatment for diabetes contributes to the manifest side effects and the shortened lifespan that people with diabetes experience. The major cause of poor results from conventional diabetes treatments is not that people with diabetes are inadequate students who simply need more education. The major problem is actually what is being taught, and this needs to be changed.
If you have lost the ability to smell an odor in a room, the best way to smell it is not to make the smell stronger (analogous to taking or making more insulin). What you should do is walk out of the room to re-sensitize your nose. When you walk back in, you can smell the odor well again, even if it has been reduced.
This is how diabetes needs to be treated. We need to reduce, not increase, the levels of insulin, so that your cells can "smell" it better. You need to reduce not just your blood sugar, but also your insulin, and the only way to do that is to get "more bang out of each insulin buck" by increasing insulin sensitivity. Contrary to what you have been told, there are no insulin sensitizing drugs. Only changing what you eat (combined perhaps with supplements that augment the dietary changes) can do this. Fortunately, changing diet does this very well, well enough to reverse most cases of type 2 diabetes completely.
Remember the laboratory changes seen in caloric-restricted diets. The longest-lived animals and people share the following traits:
- Reduction in fasting glucose
- Low fasting insulin levels
- Lower body temperature
- Low percentage of body (viceral) fat
- Reduced thyroid levels
- Low triglycerides
- Low leptin
Let's examine this further.
Your grandmother probably told you, "Sugar is bad for you," and she was absolutely correct. Why do the longest living humans and animals have low blood sugar levels for their age? First, high blood levels of sugar from nonfiber carbohydrates and excess protein send leptin levels soaring, causing leptin resistance and obesity. It's also well known that high glucose also raises insulin, and it's well documented in laboratory animals that high insulin accelerates aging. Glucose literally AGEs you.
In a process called glycation, glucose reacts with protein, resulting in sticky, sugar-damaged proteins called advanced glycated end products (AGEs). When protein is damaged, it cannot function properly or communicate properly with other cells. AGEs also promote inflammation and free radical oxidation throughout the body. AGEs cause skin to wrinkle, and wrinkling and damage to the lining of arteries contributes to plaque and heart attacks. It can promote the formation of cataracts, macular degeneration, and eventual blindness.
The glycation process has also been linked to the destruction of protein and nerve cells that can lead to Alzheimer's disease, memory loss and various neuropathies. Heating of starches (especially frying them, like french fries and chips) can produce a type of glycated protein called acrilamides, which are potent carcinogens.
Glycation, along with free radicals from oxidation, are two of the major molecular mechanisms whereby damage accrues, disease occurs and death results. A good analogy is making caramel, where you add sugar to cream - a form of glycation in which fat oxidizes and turns rancid. As we age, we "caramelize" and turn rancid. I prefer to minimize that.
High blood sugar can suppress your immune system, making you more vulnerable to infection and cancer. Glucose is very similar in molecular structure to vitamin C, confusing white blood cells and impairing their ability to gobble up invading bacteria, viruses and cancer cells. Highly aggressive cancers outpace the availability of oxygen and therefore use an anaerobic fuel - glucose. Elevating glucose just feeds this.
Insulin's Real Purpose
What about insulin? If there is a known single marker for life span, as they are finding in the centenarian and laboratory animal studies, it is low insulin levels. What is the purpose of insulin? It is not to lower blood sugar, as is believed by the general public and the medical profession alike. That is a relatively trivial side effect, as it is also the function of other hormones such as glucagon, epinephrine, cortisol and growth hormone.
Insulin's evolutionary purpose is to store excess energy for future times of need. It lowers blood glucose levels for the purpose of storing it away, not regulating it. Our ancestors were forced to survive for days, weeks, or even months on little food. High glucose was not a big problem back then! Insulin helped our ancestors store away nutrients for the proverbial rainy day when they would need it.
Today, high glucose is the norm, not the exception. As a result, our insulin levels are typically much higher than they were among our ancestors. When your cells are constantly bombarded with insulin, they become insulin resistant; that is, they stop hearing insulin's important message. Moreover, excess insulin can damage your cells. In fact, insulin resistance may be a defense mechanism on the part of cells to protect against the toxic effects of excess insulin and to keep glucose, and therefore glycation, inside cells and in check. High insulin creates a hormonal derangement that has a catastrophic effect on your metabolism.
High insulin contributes to making you fat. Why? Firstly, high insulin is telling your cells to store fat rather than burn it. More importantly, repeatedly high levels of insulin cause insulin resistance. This wouldn't be so bad if it were uniform, but the major problem, once again, is a loss in the orchestration of the signals. Not all cells become insulin-resistant at the same time.
A possible scenario follows. Liver cells may be among the first to become insulin resistant. Since one of insulin's effects is to suppress production of sugar by the liver, if the liver is no longer listening to insulin, it is going to make a lot of sugar. Eventually muscle cells will become insulin resistant too. Then they can't burn the sugar that was manufactured by the liver, so your blood sugar levels keep rising. Your fat cells are among the last to become insulin resistant, which is a real problem because insulin promotes the making and storage of fat. Thanks to insulin, all that excess sugar that hasn't been burned off is now socked away as fat!
One could consider obesity to be the price one is paying to keep from becoming diabetic. Unfortunately, diabetes is still being defined by blood glucose and not by the derangement in hormone signaling that it should be. Eventually, your fat cells will become insulin resistant, and you can then stop making all that fat. But then you have no place to put the excess sugar and it starts building up in your blood, and you finally will be diagnosed with diabetes.
Incidentally, two of the most popular diabetic medications today, Actos and Avandia, wrongly claimed by their manufactures as being insulin sensitizers, actually work by multiplying fat cells, thereby creating more wastebaskets in which to store sugar as fat. They actually make you fatter and more leptin resistant, and they accelerate your rate of aging.
High insulin is a major contributor to cardiovascular disease. It results in the inability to properly store magnesium, causing blood vessels to constrict, elevated blood pressure, and coronary arterial spasm, all of which can result in a heart attack. Also, with low magnesium you can't properly metabolize important fatty acids such as EPA and DHA, which are vital to your heart and health in general.
Excess insulin causes retention of sodium, fluid retention, elevated blood pressure and congestive heart failure. Studies have shown that if you drip insulin into the artery of an animal, the artery will become blocked with plaque. Heart attacks are much more likely to happen after a high carbohydrate meal than after a high fat meal. The immediate effect of the rise in blood sugar after a high-carb meal is to raise insulin and leptin; that, in turn, triggers a "stress response" that can cause arterial spasm, constriction of the arteries, irregular heartbeat and even sudden death.
Elevated insulin plays an important role in osteoporosis. Insulin promotes the excretion of calcium in the urine. Much more importantly, if insulin is elevated and leptin resistance is telling your brain that you mustn't burn fat, then you have no choice but to burn sugar or foods that turn to sugar for fuel. Since we store very little sugar, you will crave it, and if you do not constantly eat it (such as when you are sleeping), then your body must break down lean mass, including muscle and bone, to supply its fuel needs.
This is a major source of osteoporosis and far exceeds in importance a lack of calcium in the vast majority of people. There is a high correlation between osteoporosis and calcification of arteries. In other words, most people with osteoporosis have the calcium - it's just in the wrong places. It is being given the wrong signals about where to go.
The Link to Cancer
In most species of calorie-restricted animals, life span increases primarily as a result of a reduction in cancer rates (cancer being the number-one killer in most animals). This is not surprising. Insulin is closely related to another hormone, IGF-1, or insulin-like growth factor. As its name implies, IGF's primary function is to promote growth and cellular reproduction. There is a strong link between IGF levels and cancer (which is basically excessive cellular reproduction).
Because of its molecular similarity to IGF, insulin can trigger the same genetic message, promoting cellular reproduction and cancer. IGF, derived from growth hormone, is normally low in calorie-restricted animals. Elegant studies have shown that bringing those IGF levels up to just average levels totally negates the benefits of caloric restriction on longevity.
Finally, and perhaps most significantly, the first, and perhaps the most powerful, genetic pathway that researchers (from the University of Colorado, Harvard, MIT, and the University of California) have been able to manipulate to greatly extend lifespan in many different species of laboratory animals is the insulin pathway. Genetically forcing insulin and its cousin, IGF, to remain low greatly extends lifespan.
As critical as insulin is to your health, leptin may even be more so. New research is revealing that glucose and therefore insulin levels may be largely determined by leptin. Leptin, through the brain and hypothalamus, also controls thyroid levels and body temperature. It largely determines the accumulation of visceral fat and the ability to burn fat as indicated by triglyceride levels. It appears to control all of the other markers of longevity.
It had been previously believed that the insulin sensitivity of muscle and fat tissues were the most important factor in determining whether one would become diabetic or not. Elegant new studies are showing that the brain and liver are most important in regulating a person's blood sugar levels especially in type 2 or insulin-resistant diabetes.
It should be noted again that leptin plays a vital role in regulating the brain's hypothalamic activity which in turn regulates much of a persons "autonomic" functions; those functions that you don't necessarily think about but which determines much of your life (and health) such as body temperature, heart rate, hunger, the stress response, fat burning or storage, reproductive behavior, and newly discovered roles in bone growth and blood sugar levels. Very recent study reveals leptin's importance in directly regulating how much sugar that the liver manufactures via gluconeogenesis mostly from muscle and bone.
Many chronic diseases are now linked to excess inflammation such as heart disease and diabetes. High leptin levels are very pro-inflammatory, and leptin also helps to mediate the manufacture of other very potent inflammatory chemicals from fat cells that also play a significant role in the progression of heart disease and diabetes. It has long been known that obesity greatly increased risk for many chronic diseases, including heart disease and diabetes, but no one really knew why. Leptin appears to be the missing link.
Leptin not only determines how much fat you have, but also where that fat is deposited. When you are leptin resistant, you put that fat mostly in your belly (your viscera), causing the so-called "apple shape" that is linked to disease. Some of that fat permeates the liver, impeding the liver's ability to listen to insulin and further hastening diabetes.
Leptin plays a far more important role in your health than, for instance, cholesterol, yet how many doctors measure leptin levels in their patients? How many know their own level, know that it can be easily measured, or even know what it would mean?
Leptin helps to control the brain areas that regulate thyroid levels and the sympathetic nervous system, which also has huge impacts on blood pressure, heart disease, diabetes, osteoporosis, and aging. Leptin's stimulatory effect on the sympathetic nervous system also helps determine the adrenal stress response, including cortisol levels.
The Link to Aging
As we have seen, leptin plays a significant role in obesity, heart disease, osteoporosis, autoimmune diseases, inflammatory diseases and cancer. These are the so-called "chronic diseases of aging." Could it perhaps affect the rate of aging itself? Scientists who study the biology of aging are beginning to look at that question.
Remember, there are two endeavors, two drives, that life has been programmed since its inception to perform successfully: to eat and to reproduce. If every one of our ancestors had not succeeded in eating and reproducing, we would not be here. All of your morphological characteristics, from your hair to your toenails, are designed to help you succeed at those two activities. That is what nature wants us to do.
Nature's purpose is not necessarily to have you live a long and healthy life, but to pass on the instructions, the genes, that tell how to perpetuate life. Even so-called "paleolithic" diets, though undoubtedly far better than what is generally eaten today, were designed by nature not to help us live a long and healthy life, but to maximize reproductive success. Nature does not care much about what happens to us after we have had a sufficient chance to reproduce. That is why we die. But there are clues as to how to live a long and healthy life. And that brings us once again to fat - and leptin, and how to control it.
The primary signal that indicates how much fat is stored is leptin, and it is also leptin that allows for reproduction, or not. It has long been known that women with very little body fat, such as marathon runners, stop ovulating. There is not enough leptin being produced to permit it. In fact, leptin was recently approved as therapy to allow skinny women to reproduce.
Leptin is also instrumental in regulating body temperature, partly by controlling the rate of metabolism via its regulation of the thyroid. Metabolic rate and temperature have long been connected with longevity. Almost all mechanisms that extend lifespan in many different organisms result in lower temperature. Flowers are refrigerated at the florist to extend their lifespan. Restricting calories in animals also results in lower temperature, reduced thyroid levels, and longer life. It should be noted that reduced thyroid levels in this case are not synonymous with hypothyroidism. In the former, the body is choosing to lower thyroid hormones because it can, not because it has no choice.
Anything will dissolve faster in hot water than cold water. Extra heat dissolves, disrupts and disorganizes. It is commonly advised to "increase metabolism" and increase "thermogenesis" for health and weight loss. Yet how many of you would put a brand of gasoline in your car that was advertised to make your engine run hotter? What would that do to the life of your car? It is not an increase in metabolism that I am after; it is improved metabolic quality. That will be determined by the quality of your leptin signaling.
If it is poor, if you are insulin and leptin resistant, your metabolism is unhealthy and high in what I call "metabolic friction." If you then increase its rate, you will likely accelerate your demise. To increase the quality of your metabolism, you must be able to properly listen to insulin and especially to leptin. If your fasting blood serum level of leptin is elevated, you are likely leptin-resistant and you will not be healthy unless you correct it.
The Source of Resistance
How do people become leptin resistant? This is the subject of much research. I believe that people become leptin resistant by the same general mechanism that people become insulin resistant; by overexposure to high levels of the hormone. High blood glucose levels cause repeated surges in insulin, and this causes cells to become "insulin-resistant," which leads to further high levels of insulin and diabetes. It is much the same as being in a smelly room for a period of time. Soon, you stop being able to smell it because the signal no longer gets through.
I believe the same happens with leptin. It has been shown that as sugar gets metabolized in fat cells, fat releases surges of leptin. Those surges result in leptin-resistance, just as insulin over-exposure results in insulin-resistance. Insulin resistance leads to high glucose that then contributes to high leptin and leptin resistance, and they both conspire to make you fat and accelerate your rate of aging.
Normally leptin's function is to reduce appetite and induce fat burning (among many other functions). That is what high leptin signaling in a brain does. Low leptin in the brain is an indication to eat more and store more fat (that is, to successfully reproduce, and to live long enough to do so). However, elevated leptin in a fasting blood sample indicates leptin resistance and, probably, low leptin signaling to some parts of the brain while other parts of the brain get the full high signal. In other words, some of the brain hears only a whisper, while other parts (of the brain and periphery) get screamed at. Neither is good communication.
Low-leptin signaling to the appetite center of the brain induces the brain to want to make the body hungry, and it alters physiologic functions so as to store more fat. Ultimately, increasing fat stores should manufacture more leptin to overcome the resistance. In the meantime, however, one continues to get fat and often obese. This is similar to insulin resistance: High fasting insulin indicates low activity in some parts of the body and a disruption in insulin signaling that is being compensated for by the pancreas, which makes more insulin. What is lost, however, is the orchestration of insulin levels among various tissues. If your liver is insulin-resistant, it continues to make sugar out of protein, and if your muscles are insulin-resistant, they cannot burn that sugar.
Until your fat tissue becomes insulin-resistant, however, it continues to "hear" the high levels of insulin that are caused by the elevated sugar. Insulin's signal to fat tissue is to take that sugar, make fat out of it, and then store it. You continue to gain weight until the adipose tissue ultimately becomes resistant.
Likewise, when you become leptin-resistant as indicated by high fasting leptin, you lose the fine orchestration of hormone levels. As the appetite control center in the hypothalamus becomes leptin resistant, it cannot hear the message from leptin to curb hunger and stop storing fat. It believes, therefore, that you do not have enough fat stores and must eat more and make more fat. Also lost is the knowledge of where to put that fat, so a preponderance of it is stored in the viscera. The communication regarding where to put calcium is also disrupted, and calcium is deposited in blood vessels instead of bone.
An Orchestral Breakdown
However, it appears that the master control center of the sympathetic nervous system in the brain does not become resistant, and it continues to hear the loud messages of elevated leptin, causing overstimulation of the sympathetic nervous system. This can cause diabetes, elevated blood pressure, increases in blood coagulation and inflammation, elevated T-3 and temperature, and heart disease. Hormonal resistance is bad mainly because of the loss of the intricate orchestration of those signals, and less so because of diminished signals that can be compensated for just by "yelling louder."
Leptin resistance plays an important role in osteoporosis. If leptin is telling your brain that you mustn't burn fat, you will have no choice but to burn sugar or foods that turn to sugar for fuel. Since we store very little sugar, you will crave it, and if you do not constantly eat it (such as when you are sleeping) then your body must break down muscle and bone matrix to supply its fuel needs. This is a major source of osteoporosis and far exceeds in importance a lack of calcium in most people. There is a high correlation between osteoporosis and calcification of arteries. In other words, most people with osteoporosis have the calcium - it's just in the wrong places. It's being given the wrong signals about where to go. Taking more calcium may then not be wise.
To summarize: normally leptin is secreted acutely in response to a meal or chronically in response to increasing fat stores. In a leptin-sensitive individual, leptin will reduce hunger, increase fat burning, and reduce fat storage. However, when one is leptin-resistant, as indicated by an elevation in fasting serum leptin, the part of leptin's message that would normally reduce hunger and fat stores, and increase fat burning does not get through to the brain (mimicking low leptin), so one stays hungry and stores more fat rather than burning it. However the message to increase sympathetic nervous system activity gets through all too loudly and clearly, so one stays hungry, continues to get fat, and gets elevated sugar, insulin resistance, high blood pressure, heart disease, and accelerated aging.
How to Restore Order
When one becomes more leptin sensitive after following my diet program, as indicated by a lower fasting leptin, suddenly the brain is able to hear leptin's messages much more clearly. The now louder and more accurate message to the appetite control center and other parts of the hypothalamus is to reduce hunger and get rid of stored fat, because now the brain realizes that you have stored far too much. The lower leptin reduces the volume that the sympathetic nervous system hears. The hormone is making less "noise," but instead is allowing the orchestra to play fine music.
The only known way to re-establish proper leptin (and insulin) signaling is to prevent those surges, and the only known way to do that is via diet and supplements. As such, these can have a more profound effect on your health than any other known modality of medical treatment. When leptin signaling is restored, your brain can finally hear the message that perhaps should have been delivered decades ago. High leptin levels can now scream to and be heard by your brain that you have too much fat and that you better start burning some off, for your life is in danger.
Your brain will finally allow you into the pantry where you have been storing your fat. Your cells will be fed the food from that fat and they will be satisfied. They will not know whether that food came from your belly fat or from your mouth, nor will they care. They will be receiving energy that they need and will not have to ask for more. You will not be hungry. This also makes counting calories irrelevant, for the calories that you put into your mouth today are not necessarily what your cells will be eating: That will be determined primarily by leptin.
Whether or not you put food into your mouth, your cells will be eating. If they cannot eat fat, they must eat sugar. Since little sugar is stored, that sugar will be obtained by making you crave it or by turning the protein in your muscle and bone into sugar. This contributes in a major way to weakness and osteoporosis. Whether or not this lean tissue wasting happens is determined by your capacity, or incapacity, to burn fat. And that is determined by your ability to listen to leptin.
A strategic diet that emphasizes good fats and avoids blood sugar spikes coupled with targeted supplements (as recommended in my Rosedale Diet), will enhance insulin and leptin sensitivity so that you can once again hear their music, allowing your life to be the symphony it was meant to be.