Hormones & Methylation

Cortisol Response

Cortisol is a glucocorticoid hormone. It is the most important one in humans, produced by the adrenal cortex and participates in the body's homeostasis and stress responses. Cortisol concentrations also follow a circadian rhythm. It is a more complex rhythm than the human melatonin rhythm. Unlike the melatonin rhythm, human cortisol rhythms do not seem to be totally associated with day and night per se, but seem to be more closely tied to the "transition periods" from dark to light and to a lesser extent, from light to dark. Transitioning light levels play a tremendous role in cortisol rhythms in humans. In addition to its circadian rhythm exhibiting a predictable peak in the morning, cortisol levels typically elevate sharply in the morning, 30 minutes to an hour after awakening. The glucocorticoid levels synthesized by the adrenal gland across the 24 hour day appear to be under the control of two distinct systems, one governed by the hypothalamic-pituitary-adrenal (HPA) axis, and one controlled by the autonomic nervous system through the adrenal medulla. Evidence supports that cortisol production can be uncoupled from the HPA axis controller of its release (ACTH). Night time light stimulates the suprachiasmatic nucleus (SCN) and this sends a neural signal to the autonomic systems to increase cortisol production from the adrenal gland, but not the brain. This is not coupled to pulsatile ACTH release in the pituitary, and has separate neural pathways. Studies have shown that exposure to high levels of polychromatic (white) light (80lux at the cornea) in the morning, but not in the evening, could increase cortisol levels in humans. It appears the intensity of light is critical to the real effect on cortisol levels. Studies have also shown that morning light can increase heart rate, suggesting an impact of light on the autonomic nervous system that modulates cortisol release from the adrenal gland. More recent studies have shown bright light to dramatically reduces cortisol levels in humans.

So You Completed The Leptin Rx? What’s Next?

Once you have added the Leptin Rx to your paleo/primal template and you have successfully experienced all the "small wins" that I mentioned in the Leptin FAQ's blog, what should you do next? If you recall reading the blog on how the leptin Rx works, it basically is a plan to make your gastrointestinal tract perform visceral exercises that it is not accustomed to performing, in order to cause neuroplastic changes in your hypothalamus' arcuate nucleus. It uses the vagus nerve as the "stimulator" to send these new messages to the brain. After a period of time, the inflammation will slowly dissipate at the median eminence, and these afferent signals will force expression of certain genes that have been repressed since we were in utero. These genes and pathways are hardwired into our DNA at conception, and used until the child is 12-24 months old. After this time, they are not expressed any longer, because transgenerational epigenetics favors instead the use of the leptin receptor from an evolutionary perspective. This occurs because the leptin receptor in the arcuate nucleus is far more sensitive and accurate in accounting for electrons from food than was using older circadian and ultradian cycles that we used in uteri during morphogenesis. The human brain learns "what neural circuits" to use by repetitive firing. We have a saying in brain surgery, nerves that fire together wire together. This is the basis of the theory of Hebbian learning. These exercises I told you about in the Leptin Rx signal hypothalamic neurons to adapt to these visceral responses to food in a new way, to sensitize the leptin receptor in order to account for electrons from food in precisely how it was designed to do by evolution. In essence, we are altering the genetic expression of the genes in our arcuate nucleus. I describe it to my patients as "performing brain surgery on them without using a blade." The visceral responses to the Leptin Rx are transcribed by the vagus nerve, and this information is sent to the brain. This message is dramatically different than the one the patient is used to giving the leptin receptor, and the new message induces changes to the neuropeptides in the brainstem. After some time, (6-8 weeks for most) changes will be induced. These can be followed by the clinician or the patient. Those clinical signs are outlined in the Leptin FAQ blog post. In doing this, we force the neurons to see neurochemical signals that radically confuse the leptin receptor and the brain. The brain's response to a signal it does not understand is to revert to an older known pathway or to learn a new way to tackle on old problem. I would suggest you watch How your brain re-learns from 2007 by Dr. VS Ramachandran in a TED talk. He exquisitely explains how this type of learning is stimulated in the brain for phantom limb pain and its treatment. One need not use expensive technology to induce gene expression. It is possible to do without an NIH grant too. It requires some synthesis of thought and experience. When you understand the essence of how the brain works, you just need to design a program and force it upon the brain to decipher what to do. That is the essence of the Leptin Rx reset.

The Osteoporosis Rx

Osteoporosis is a disease in which the bones become weak and are more likely to break. People with osteoporosis most often break bones in the hip, spine, and wrist. If you think this problem is not common, let me pick up the rock you must have been sleeping under. In the United States, more than 60 million people either already have osteoporosis or are at high risk, due to low bone mass. RULE 1. If one is leptin resistant, Wolff’s law is null and void, and you are at very high risk for a fractured vertebrae or hip/wrist. You should stop here and go read EMF-8 Quantum Bone for the pathophysiology of this disease. The key features are to increase your spring water intake to 1-1.5 gallons of non fluoridated water a day and strict avoidance of artifical light and the use of pulsed EMF technology devices. This means that "normal conventional wisdom osteoporotic treatments" and exercise will not heal or strengthen a bone until the underlyig pathophysiology is repaired first. When a person has high levels of leptin, it eventually drives cortisol higher and this stimulates even more inflammatory cytokines from cells. As this occurs, LR develops all over the body. Cortisol is one of the major hormones involved in the sympathetic nervous system. When cortisol is chronically high, as I told you in the Hormone 101 blog, it’s bad news. When someone is leptin resistant, they block osteocalcin’s main function and this causes osteoporosis. This is one major reason why fat people lose their bone. It also definitely proves that Wolff’s law is null and void when you are LR. Even resistance exercise maybe harmful when this occurs. Bone only strengthens when the underlying hormonal terroir is working properly. In LR, it is seriously broken. RULE 2. Andropause and Menopause are associated with osteoporosis, and not caused by it. In both situations the best treatment to overcome it is to change your diet to a high fat and protein diet. You would be a wise patient to avoid all bisphosphonate drugs until it’s too late. This will be hard to do, because most clinicians will push drug treatments over evolutionary medicine treatments. Remember The Seven Dwarfs of menopause: Itchy, bitchy, sleepy, sweaty, bloated, forgetful, and all dried up…and the bones are real dried up!

Osteoporosis 3: Related Drugs and Diseases

What are some of the medical conditions that are associated with osteopenia or osteoporosis? 1. Excessive alcohol intake- greater than two drinks a day consistently will do it. 2. Tobacco use- This causes a 100 fold increase in bone loss. Oral tobacco is worse than inhaled smoke 3. Stress- any cause be it emotional, physical, mental, psychic all raise cortisol chronically and kill bone 4. Lack of physical activity increases obesity risk, which increases cortisol from leptin resistance 5. Low calcium intake or absorption from gastrectomy or low acid production from any reason 6. Reduced strength and activity due to a chronic illness or a sedentary life (checked with a grip test) 7. Small build or leanness naturally – correlates with BMI below 19 for women and men. 8. Asian women have a particular propensity to osteopenia genetically and from their diet. 9. Drug therapy, for example, long-term use of corticosteroids such as prednisone-used to treat rheumatoid arthritis, asthma, celiac disease, autoimmune diseases, Crohn’s disease, IBD, and ulcerative colitis. 10. Low Magnesium, strontium, boron, Vitamin D3, Vitamin K2, elevated PTH levels, low sex steroid levels, high insulin levels, low progesterone levels, any cause of a leaky gut. 11. Menopause 12. Andropause 13. Any cause of chronic inflammation (perimenopause can cause severe acute bone loss) 14. Disuse atrophy from any cause (space travel) 15. Paralysis 16. High carbohydrate diets 17. Veganism or a plant based diet. 18. A diet high in whole grain (carbohydrates) is especially risky due to mineral malabsorption in gut 19. A diet lacking in animal protein and animal fat and cholesterol. 20. Excessive use of statins and thyroid hormone can cause osteoporosis 21. Age and sex: the older one is predisposes to osteopenia. Women lose 1-3{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of their bone density ever year after their last period. 22. Chronic endurance athletics of any type cause severe bone loss due to chronic cortisol elevations 23. Gastric bypass patients carry enormous osteopenic risks. 24. Severe liver or kidney disease; Renal insufficiency can lead to osteodystrophy. 25. Diabetes 26. People with scoliosis of unknown cause (idiopathic scoliosis) also have a higher risk of osteoporosis. I believe this is because most of these children have severe underlying Vitamin D deficiency and a leaky gut, but this has never been studied in the spine literature. Any time I see a scolisosi patient, I always screen for low sex steroid hormones, low Vitamin D levels, and low Carboxylated osteocalcin levels. Bone loss can be a feature of complex regional pain syndromes.as they develop over time. It is also more frequent in people with Parkinson’s disease and chronic obstructive pulmonary disease as well.

Osteoporosis 2: The Vitamin K2 Story

In the first blog on osteoporosis, we focused in on how to stimulate bone mass accrual via our diet. This is by far the best way to fight osteoporosis and least used way, but it is not the only way to treat it. Eating a diet that is plentiful in proteins and saturated fats are smart moves to stave off bone loss as one ages. Eating a diet laden in carbohydrates or filled with a lot of fowl like turkey and chicken is not going to help your bone mass in the long run. The last blog demonstrated that vitamin K2 supplementation (for just 4 weeks) will not only increase your insulin sensitivity, but raise your sex steroid hormones as well to support your bone metabolism. Both mechanisms seem to be related to increased amounts of serum carboxylated osteocalcin (cOC), is made rather than just modulating inflammation in our body. The study I mentioned in part one, had too small a sample size to make firm interpretation on β-cell function result for a population, but the implications are huge for T2D with bad bone, bad heart or bad teeth. It is clear that vitamin K2 is biochemically quite helpful to a T2D with bone loss. The results of this study are consistent with previous studies found in the literature that demonstrated improved insulin resistance by treatment with vitamin K1 or vitamin K2, respectively. The preponderance of the research to date, is pointing out to us that cOC rather than uncarboxylated OC, is the endocrine hormone that increases insulin sensitivity in humans and eventually leads to increased bone mass. It appears the underlying mechanism for this uses inflammatory cytokines and involves leptin receptor dysfunction. It appears that cOC and/or vitamin K2 likely modulates several adipokines and inflammatory pathways other than the classic IL-6 pathways to offset bone loss seen in leptin receptor disease states. Since Vitamin K2 is a critical component of arterial, gut, and bone health, we need to spend some time talking about how the human body handles vitamin K2 in part two of this series. Vitamin K2 up regulates testosterone and it helps both sexes remain somewhat hydrated. This will become important when we hit quantum biology in the blog.

Osteoporosis Part 1

In my day job as a neurosurgeon, I operate on a lot of diseased spines. In the last 12 years, I have repaired over 1000 vertebral fractures from osteoporosis. If you remember back to my podcast with Jimmy Moore, I mentioned in the talk that the changes I had seen in osteoporosis incidence and prevalence is what made me look for the underlying cause. This ultimately led me to leptin and our diet. Many people think since bones are hard and used for support that they are not an active tissue. Bone is a very active tissue in the body that is constantly turned over. We constantly lay down new bone to stressors and resorb bone from areas that are not stressed. Since bone is so active, it uses massive amounts of energy. This is where leptin comes in. Any tissue that requires a ton of energy is coupled to leptin biochemistry. The story on bones and osteoporosis, however, is a very complicated one. I am going to give you a flavor of just how complicated. This osteoporosis series will have many twists and turns. Most seasoned spine surgeons wont know much of what you are going to learn here about bone. Most don't know that osteoporosis is caused by leptin resistance. Just ask one and see if I am correct. Most will tell you to take Calcium, Vitamin D, and exercise a bit to treat osteoporosis. They may mention a Rx for a bisphosphonate class of drugs too. I don't use these drugs at all. If you do just that, you can bet you won't cure a thing and you might even make the problem worse. Spine surgeons are taught a law called Wolff's law in reference to bone metabolism. It says the more stressed a bone is, the more bone is laid down and the stronger the bone is. This law is why most spine surgeons don't think that obese folks will have osteoporosis when they come to see us, much less test for it. These are the people who are experiencing a silent epidemic of this condition. Their numbers have exploded over the last thirty years. I mentioned that in my career I have seen a tremendous increase in this disease. In medical school, I think I had a one hour lecture on this disease. Now it is involved in close to 80{a7b724a0454d92c70890dedf5ec22a026af4df067c7b55aa6009b4d34d5da3c6} of the cases I see in my clinic. Few spine surgeons expect to see osteoporosis in our younger patients because most think this is predominantly a disease of old women with low estrogen levels. We are not taught to look for it in its correct biologic context, so it is often missed as a diagnosis, but often found on MRI imaging as loss of mineral content and more fat present in the marrow space. Spine surgeons must be more vigilant about this disease, because if it's tied to the leptin hormone, it points to the fuels we are putting in our Ferrari's! I will show you why diet is a huge factor in the development of metabolic bone disease that you should consider. This is why I treat osteopenia and osteoporosis a lot differently than conventional wisdom you will hear from other sources.

How Does The Leptin Rx Work?

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.

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