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Ghrelin The Hunger Hormone


Ghrelin Hormone Guide

What is Ghrelin?

Ghrelin is the primary hormone in the human body which regulates the sensation of hunger. It is considered a partner to a hormone known as Leptin, which controls satiation. Whereas Leptin is produced primarily by adipose fat tissue, Ghrelin is released by special cells throughout the digestive system. After Ghrelin is released, the hormone circulates through the body and activates at sites throughout the nervous system, in particular, the hypothalamus.

Like Leptin, in addition to impacting hunger signals, Ghrelin also has a role in metabolism and the usage and storage of energy.

When is Ghrelin Released?

Ghrelin is produced by the stomach when the stomach is empty, and the release of the hormone is suppressed when the stomach is stretched. The primary influence of Ghrelin is upon the hypothalamus, where it triggers the sensation of hunger and encourages the stomach to release acid in preparation of its next meal. It also readies the entire digestive system to process and move food through the system.

Leptin and Ghrelin both trigger activity upon the same receptors in the hypothalamus, although Ghrelin encourages hunger and Leptin suppresses it.

Ghrelin also alters the sensitivity of a certain pleasure center of the brain known as the ventral tegmental area, an area which plays a major role in both addiction and sexual libido. In particular, Ghrelin has a powerful influence on both acetylcholine and dopamine production.

Ghrelin is just one of many hormones that help human beings (and other animals) establish a routine pattern of energy distribution. It encourages the body to intake calories which will be converted into energy by stimulating hunger, and also alters the way that the body uses energy, in terms of immediate heat generation, adipose fat storage, and the process of the ATP cycle.

Ghrelin and Leptin Ideally Create Metabolic Homeostasis

When Ghrelin and Leptin are interacting as they should, it helps to promote an ideal physiological state, but when these hormones get out of their natural rhythms, it can lead to increased body weight and reduced metabolism, as well as powerful sensations of hunger which encourage eating junk food and other foods dense in calories.

Leptin controls the way that the body responds to food via signals from body fat, while Ghrelin controls the way that the body responds to food from the stomach itself. There are a number of pathways through which Ghrelin achieves this, some of which are not fully understood at this time. There are also synthetic molecules which imitate the function of Ghrelin which have the ability to both promote weight gain and increase appetite by activating receptor sites on the arcuate nucleus.

Insulin, Leptin, and Ghrelin

The ability of Ghrelin receptors to accept stimulation is affected both by the influence of insulin and Leptin. Also, Ghrelin encourages eating full meals because it suppresses the body's ability to feel the stomach stretch until toward the end of the meal when Ghrelin levels decline.

In addition to directly controlling hunger, Ghrelin also promotes the release of pleasure hormones which encourage an individual to regularly eat, but can also promote overeating as well as addiction if a patient lacks willpower and self-control. In fact, alcohol dependency requires Ghrelin to activate receptors on the hypothalamus, and this is also one of the influences which encourage people to prefer certain foods over others.

Ghrelin and Eating Habits

Ghrelin is a powerful hormonal force which controls both feeding and appetite in animals, including humans. Ghrelin levels drop after we eat a meal, and slowly rise over time, increasing our hunger and desire to eat. Ghrelin peaks immediately before eating and drops to its lowest levels after the meal has concluded.

Ghrelin Injections, and the injection of Synthetic Ghrelin Analogues, have the ability to increase hunger and appetite dependent upon the dose of the hormone that is administered. This means that the more Ghrelin that is administered, the more calories that a patient will consume over time. This does not make individuals eat more at every meal, however. It makes them become hungry again much more quickly than they normally would, so they eat more meals each day.

In animal species, the administration of Ghrelin causes the animal to search for food more aggressively, and increases the prevalence of any activities related to meal habits, including hoarding, foraging, or sniffing out food.

Ghrelin and Metabolism

Body mass is controlled through metabolism. At its simplest, this simply means that weight is controlled by adjusting how calories are taken in and how calories are burned from day to day. The more Ghrelin that an animal produces, the more they will weigh, as a general rule. Based on this information, it is believed that Ghrelin acts as an intermediary between adipose fat deposits and the brain.

Ghrelin is dependent upon the weight of the individual. The less than a person weights, the more Ghrelin that their body will produce, while on the other hand, the more that a person weighs, the less Ghrelin that they will produce. This may be one reason why many people that are overweight don't eat as often as their peers, but eat larger meals as a result of their lack of self control.

Under normal circumstances, Ghrelin works in the body as a means to keep weight at an average healthy level, mediating the body's use of energy and its mass.

Ghrelin and the Digestive System

Ghrelin acts as an anti-inflammatory in the digestive system and prevents cells from spontaneously dying during times of internal stress and inflammation. Ghrelin generally promotes the activity of other anti-inflammatory hormones and compounds while limiting the activity of those that cause inflammation. For this reason, researchers hypothesize that medically administered Ghrelin may one day be useful in promoting gastrointestinal health during these times of stress. Ghrelin also appears to help the interior of the digestive system rehabilitate itself after damage and injury.

In the case of pancreatic and gastrointestinal cancers, elevated Ghrelin levels can exacerbate the illness.

Ghrelin and the Pancreas

Ghrelin and insulin are related hormones, and the presence of one impacts the activity of the other. There are Ghrelin receptors on the pancreas, and when Ghrelin activates these points, it slows down the release of insulin in response to the presence of glucose. This means that Ghrelin slows down the rate at which the body processes sugar as it circulates through the body.

Ghrelin and Heart Health

Ghrelin is beneficial to heart health because it inhibits the formation of fatty deposits in the arteries, and it also encourages the healthy function of the endothelium, the inner lining of the blood vessels.

Ghrelin, Memory, and Learning

The hippocampus is the center for learning in the brain. Ghrelin plays a role in all of this, and also encourages the production of Human Growth Hormone. Ghrelin circulates through the blood stream and passes through the blood-brain barrier at the hippocampus, and encourages the development of new connections in the brain

There is some evidence that the brain is able to retain information at the highest levels when Ghrelin levels are higher, which means that when people are full, they may have slightly more trouble learning than when they are hungry. From an evolutionary perspective, it does seem beneficial to have additional horsepower in the brain when the body requires food, and for the mind to slow down after a meal has been found and consumed. This process is apparent in animal studies, and it is hypothesized that in humans this same mechanism is at play, at least to a certain extent.

Ghrelin and Depression

Animal research has shown that Ghrelin promotes a healthier psychological profile and inhibits depression. Lab mice which don't produce Ghrelin experience greater levels of anxiety when they are exposed to both physical and psychological stress. Under normal circumstances, Ghrelin has the ability to interact with the hypothalamic-pituitary-adrenal axis in a way that reduces the effects of stress.

Also, animal studies have shown that Ghrelin acts like an anti-depressant in laboratory mice, as rodents with elevated levels of the hormone showed fewer signs of stress than their peers without Ghrelin. Furthermore, rodents that were unable to produce Ghrelin were less likely to interact with other rats around them.

When these lab rodents were provided an anti-depressant, it counteracted the social inhibition experienced resulting from a lack of Ghrelin, which suggests that Ghrelin helps ward off depression by some underlying mechanism.

Ghrelin and Sleep

Elevated Ghrelin Levels are associated with shorter periods of rest, and this is also associated with being overweight. The more Ghrelin that is present in the blood stream, the less sleep that an individual will experience. Also, those that sleep well through the night are less likely to experience obesity, and their Ghrelin levels tend to be lower.

Ghrelin and Fear Response

Humans and animals have a tendency to experience latent fear as a result of past experiences of stress. Ghrelin plays a role in this, as the body releases Ghrelin in response to such fear, which makes the source of the fear easier to retain. Stress affects Ghrelin concentrations even when the body is not producing adrenal hormones such as cortisol. When Ghrelin stimulation is inhibited, this suppresses the brain's tendency to learn what to fear more effectively under stress, although it does not affect adrenal response to stress.

In the future, there will likely be medications that use synthetic Ghrelin or Ghrelin analogues as a means to limit the effects of mental disorders caused by stress.

Ghrelin and Dopamine

Dopamine is the primary pleasure hormone that is produced by the body. Ghrelin increases the level of dopamine that is present in the substantia nigra, which is the reward center of the brain. Upon eating or engaging in any other pleasurable activity, this enhances the sensation of pleasure.

Ghrelin and Reproductive Health

Ghrelin inhibits the release of precursor hormones which produce sex hormones and sperm, whereas Leptin encourages the production of these hormones. It is unclear to what extent that this may limit fertility. From an evolutionary standpoint, it makes sense that during times of hunger, reproduction would be a secondary concern, whereas during periods of satiation and abundance, sex drive and function would increase.

Prenatal Health and Ghrelin Production

During the fetal stage, the developing lungs produce Ghrelin in order to accelerate the growth of the organ. Also, there is a connection between the concentration of Ghrelin in the umbilical cord and the weight of the child at birth.

Ghrelin, Obesity, and Anorexia

As we mentioned earlier, individuals that are overweight or obese do not produce as much Ghrelin as their thinner counterparts. For this reason, it does not seem that Ghrelin is a contributor to weight gain, although its high or low levels can affect other aspects of physiological health. The exception to this is patients that suffer from Prader-Willi syndrome. Among these patients, Ghrelin levels do promote obesity.

Individuals that suffer from anorexia have exceptionally high blood-concentrations of Ghrelin. The issue is that their bodies override these normal physiological cues to eat. Clinical research has shown that by introducing exogenous Ghrelin intravenously, it is possible to increase calorie intake among patients with anorexia by as much as 36%.

Under normal, healthy circumstances, Ghrelin levels are low around bedtime and increase slowly through the course of the night. Overweight and obese individuals are more likely to experience elevated Ghrelin levels at inappropriate times, which is evidence toward the hypothesis that obesity is a condition that is exacerbated by an incorrect circadian rhythm.

Being in front of a computer screen or other source of abundant light during the late evening can interrupt the natural rise and fall or Ghrelin levels at night. Also, individuals that don't get enough sleep at night produce more Ghrelin, because sleep naturally has a depressant effect upon the hormone. Poor sleeping habits promote the suppression of leptin and the release of Ghrelin, which promotes overeating.

Potential Medical Uses of Ghrelin in the Future

  • Ghrelin may also prove to be an effective means to promote the normal muscle activity of the stomach in individuals suffering from gastroparesis.

  • In animal research, Ghrelin has proven effective at reducing the number and severity of seizures that afflicted animals experience. This may cross over into humans.

  • Ghrelin will soon be used as a treatment for many forms of wasting disease, and may assist patients being treated for kidney failure.

Ghrelin and Appetite: A Research Study

New research shows that elevated levels of Ghrelin promote poor dietary choices, which is why many people may be more prone to eating unhealthy foods packed with calories like cookies and cake.

Simply having elevated Ghrelin in circulation is as powerful of an influence on diet as the act of fasting, both of which encourage desire for calorie-dense foods. Ghrelin reaches very high levels during the act of fasting, but the administration of synthetic Ghrelin can mimic the physiological and psychological desires associated with such a fast, even if the patient does not engage in the activity.

This is because of the way that Ghrelin interacts with the reward centers of the brain. In this study, it was found that synthetic Ghrelin significantly increased the activity in the area of the brain which activates in response to pleasure.

The main researcher in this study, Dr. Goldstone, was interested in seeing how the administration of Ghrelin via injection compared to the act of fasting in relationship to dietary choice.

His study involved eighteen patients, all around the age of 23, all of which were of average weight. They were required to fast the night before and come in without breakfast, and they visited the medical location on three occasions, all of which were at least seven days between.

Each visit, patients either stayed on the fast or ate a meal of 730 calories. After they were fed or required to remain on their fast, they were administered with an injection of either Ghrelin or saline. In order to ensure that the patients' bodies reacted to the Ghrelin injection, they were tested for elevated HGH levels, which rise at the same time that Ghrelin Levels rise in the blood stream.

Ghrelin Research Procedures

Rather than eating after the injection, the subjects were shown various images of foods, sixty of which were low calorie foods, and sixty of which were foods with high calories. Interspersed among these pictures were photos of things seen around the house, to act as a control. During this rating process, their brains were scanned in an MRI machine, meaning that the patient could both provide a qualitative response while the researchers also measured the neurological response to the food stimulus.

How Does Ghrelin Affect Desire for Food?

What researchers discovered was that Ghrelin had no effect on the participants' interest in foods with low calories, while it did increase the desire for foods with a lot of calories. In particular, Ghrelin increased the desire for sweets the most.

One particular area of the brain that was closely monitored during these tests was the anterior orbital frontal cortex, which is the location of the brain that stores the desire that the brain has for particular foods. He found that satiated individuals that received saline did not experience high levels of activation in this area, whereas those that received Ghrelin still experienced activity in this area even when the patient was fed prior to the imaging session.

Does Ghrelin Contribute to Obesity?

Ghrelin may not directly cause obesity, but it does prevent the body from changing its pattern of nutrition intake. Ghrelin levels remain low as long as the obese patient stays at his or her stable weight, but as soon as he or she tries to lose the weight, Ghrelin levels increase dramatically. It is believed that one day, there will be treatments available which block the body's production of Ghrelin during dieting in order to promote weight loss and treat obesity.

References:

Hormone Ghrelin Ups Desire for High Calorie Foods

http://www.webmd.com/diet/news/20100622/hormone-ghrelin-ups-desire-for-high-calorie-foods

Wikipedia: Ghrelin

http://en.wikipedia.org/wiki/Ghrelin

Your Hunger Hormones: How They Affect Your Appetite and Your Weight

http://www.webmd.com/diet/features/your-hunger-hormones

19 August 2014

Leptin Hormone Guide: The Effects of the Satiety Hormone


Leptin Hormone Guide

What is Leptin?

Leptin is a hormone that has many purposes, but primarily it is responsible for the full sensation that we get after the body decides that we've had enough to eat. It is frequently referred to as the “satiety hormone.” Leptin is released by fat cells in an effort to control the way that our body stores fat. In addition to suppressing hunger, leptin also alters the way that our body uses energy.

The fat cells release leptin when they have stored a certain level of fat converted from the calories from the food that we eat. When leptin is released, it enters the blood stream and passes through the body. Leptin travels through the cardiovascular system to the hypothalamus, where it activates special receptors in the arcuate nucleus.

When leptin receptors are activated, it causes the body to increase metabolism, while also reducing signals for hunger. Although this is primarily affected through the brain, there are targets throughout the body which are also responsible for increasing metabolism.

The two hormones, Leptin and Ghrelin, have opposite, component effects upon the body. Whereas leptin controls the feeling of satiation, Ghrelin controls the sensation of hunger. Leptin and Ghrelin receptors are actually located on the same cells, and are two vital hormones responsible for the way that our body both stores and expends energy.

Leptin has a number of different purposes in the body, but the most important of these is considered the regulation of the way that the body stores fat. Our knowledge of how Leptin works is far from complete, but leptin is produced not only by fat cells, but by other organs as well.

Where is Leptin Produced?

The majority of leptin is secreted by white adipose fat tissue by organelles known as adipocytes. Leptin is also secreted from other locations, including the liver, pituitary, bone marrow, epithelial cells, stomach, skeletal muscle, ovaries, placenta, and brown adipose fat tissue.

What Causes Leptin Levels to Fluctuate?

Like other hormones such as Testosterone, Leptin flows through the blood stream both locked into a carrier protein and freely. Because body fat produces leptin, the more body fat that a person carries, the more leptin that they will produce. Perhaps surprisingly, the amount of leptin produced by body fat increases exponentially with the volume of body fat that a person carries.

Leptin concentrations also follow the circadian rhythm under normal circumstances. From around 12am to some point in the early morning, leptin levels remain quite high, which is believed to prevent hunger and promote sleep. Although this is the normal pattern of leptin release and circulation, if a person eats at odd times, such as in the middle of the night, this alters the rhythm of leptin release.

There are many ways that Leptin production is unrelated to body fat as well:

  • Fasting for one to three days leads to a drop in Leptin production, even if body fat remains the same. Related to this, Leptin levels also drop as a response to starvation, encouraging hunger even when the body still has a large amount of body fat. This is actually one reason why crash diets don't work effectively. Starving yourself will eventually cause you to lose weight, but once you lose the weight, your body will not be able to effectively send signals for satiation, causing you to eat more than your body needs and experience hunger even though you are eating a healthy diet.

  • Psychological stress increases Leptin Production.

  • Leptin is affected significantly by sex hormone concentrations in the body. Testosterone is associated with reduced leptin, whereas estrogen is associated with increased leptin. Some hormones released in response to stress, including dexamethasone, also increase leptin secretion.

  • Physical training will cause leptin levels to drop for the duration of time that a person engages in a healthy exercise routine. This makes sense, because physical exercise stimulates metabolism and increases the need for calories to maintain a certain weight.

  • The more insulin that your body produces, the more leptin that your body will produce.

  • For complex reasons, obesity actually leads to an increase in Leptin production.

  • Overweight individuals with obstructive sleep apnea experience increased leptin levels, but CPAP treatment can bring leptin production back to more normalized levels. Short-term sleep deprivation can lead to a reduction in Leptin production, but long term issues with sleep deprivation, such as sleep apnea, can increase leptin concentrations.

Effects of Leptin

After Leptin is released by body fat and other cells, it suppresses hunger primarily through three mechanisms:

  • Encourages the production of α-MSH, which suppresses hunger.

  • Blocks the activity of anandamide, a hormone which encourages hunger via the same mechanism as THC present in marijuana.

  • Blocks the activity of Neuropeptide Y, a molecule released by the hypothalamus and the stomach which encourages hunger.

In spite of the fact that leptin is the hormone that we most associate with hunger, it is actually only responsible for long-term appetite control. Other hormones are responsible for short term and intermediate hunger:

  • PYY3-36 is the reason why we don't feel hungry between meals. This hormone encourages us to eat our meals during single sittings.

  • Cholecystokinin is the hormone which is produced as we eat which inhibits hunger signals. This hormone helps us know when we are full at a particular meal.

Of course, leptin does play a role in the way that these hormones function. Animal research involving leptin clearly shows how the hormone contributes to diet control, as animals which have their ability to produce leptin removed gain weight uncontrollably as a result of a loss of their ability to become full.

Caloric restriction and fasting both have an inhibitive effect upon the production of Leptin. In addition to this, the body is more reactive to the absence of food, rather than its overabundance, so Leptin production will change faster and more dramatically when the body is not getting enough food. This also means that once food access is restored, hunger response won't return to normal as quickly as it was first altered.

Changes in leptin production resulting from abrupt changes in food access appear to be correlated with changes in food intake and diet rather than the energy available that is locked in body fat. This means that leptin suppression due to hunger is not mitigated by existing body fat.

How Does Leptin Control Diet?

Leptin encourages eating and changes in metabolism by triggering receptors in the mediobasal hypothalamus. It used to be believed that blood sugar directly controlled metabolism and eating patterns, but it is clear today that leptin is the mediator of this process.

As we mentioned earlier, Neuropeptide Y activity encourages hunger. There are neurons which produce this hormone in the arcuate nucleus, and as leptin passes through the body, it binds to these neurons, preventing the release of this potent hunger hormone, promoting a disinterest in food. There is also evidence that when Leptin levels are in balance, this makes it easier to eat a healthy diet and not be tempted by the allure of calorie-dense foods.

Prior research has shown that Neuropeptide Y plays an important role in the way that animals eat, including humans. When Neuropeptide Y is artificially introduced to the brain, it automatically triggers the animal to seek out food. The opposite is also true. If the neurons which produce Neuropeptide Y are destroyed, the mice ill become disinterested in eating and become drastically underweight.

Leptin also encourages the release of a peptide known as α-MSH which promotes the feeling of satiety, and genetic abnormalities which limit α-MSH have been shown to increase hunger response and increase the risk of obesity considerably.

Melatonin Affects Leptin Production

In a vacuum, elevated melatonin leads directly to reduced production of leptin. On the other hand, if insulin is in circulation, melatonin leads to an increase in leptin production. This interaction is important because it prevents us from becoming hungry while we are asleep, which can disturb sleeping patterns.

This is why it is generally encouraged to eat a healthy dinner a few hours before bed. This way, your stomach isn't full while you are asleep, but your digestive system is still somewhat active, which means that you have insulin and melatonin in your blood stream, which encourages healthy sleep.

By the end of the night, when insulin levels drop, Leptin levels start to fall as well, as melatonin levels are still elevated. This, in combination with an increase in cortisol and other factors, helps set the stage for you to wake up refreshed and hungry.

Leptin and Diabetes

Preliminary animal research shows that combining leptin with insulin improves metabolism and stabilizes blood sugar more effectively. This combination also helped promote healthier body composition while also balancing cholesterol.

Leptin and the Cardiovascular System

Leptin has an impact on the activity of T-Cells in the immune system. Leptin promotes the health of the heart tissue and healthy leptin levels reduce the inflammatory activity which promotes atherosclerosis. There is also evidence that elevated Leptin levels can help control blood pressure if prescribed medically.

Leptin and the Reproductive System

Leptin does not play any predominant role in human fertility, but it is important and necessary to create the conditions which promote fertility. The regularity of the menstrual cycle depends upon proper metabolism, and is dependent upon the normalized flow of energy through the body, which leptin plays a part in regulating.

If a woman frequently enters a state of starvation, whether purposefully or unintentionally, the menstrual cycle will go into dormancy. Also, if a woman engages in heavy exercise, they also risk entering this state, even if they consume enough calories to meet the demands of their body. On the other hand, menstruation is only affected by low body mass in extreme cases.

In both sexes, Leptin encourages the hypothalamus to produce Gonadotropin-Releasing Hormone, the precursor to Luteinizing Hormone and Follicle-Stimulating Hormone necessary to encourage both sex hormone production as well as sperm production.

Leptin and Pregnancy

During pregnancy, leptin is produced by the placenta, and it continues to be produced in greater concentration throughout pregnancy before returning to baseline after the child is born. This is because leptin has an inhibitory effect upon contractions, allowing the child to develop within the womb. When leptin levels fall, this encourages contractions and helps to stimulate childbirth. Elevated leptin levels also contribute to the condition of morning sickness that commonly takes place during pregnancy.

Leptin and Puberty

There are two hormones which determine when an individual enters puberty: kisspeptin and leptin. In the period just before puberty, leptin levels start to rise, and once they reach a certain point, puberty is triggered. Childhood obesity can lead to early puberty, because adipose fat cells produce leptin, and cause leptin levels to reach the triggering point much faster than in children with normal levels of body fat. There is also evidence that girls that enter puberty early don't grow as tall as their peers, because the increase in estrogen production promotes the closure of the growth plates.

Leptin and Bone Mineral Density

Leptin also appears to help promote healthy bone mineral density. When the brain receives sufficient satiation signals, it then signals the bones to undergo metabolic changes which promote cortical bone growth and inhibit cancellous bone. Cancellous bone is the softer tissue in the core of the bone, and cortical bone is the hard casing which covers the cancellous bone. Thus, leptin plays a role in bone maturation during puberty because the bones become thicker and harder, allowing them to carry more weight.

After puberty, leptin still plays a role in bone metabolism, because once it activates at its receptor sites on the hypothalamus, is alters the production of a number of other hormones and peptides associated with the regulation of bone mineral density. There is also some evidence that Leptin directly contributes to increased bone mineral density by playing an intermediary role between metabolism and the release and activation of Insulin-Like Growth Factor-One. As a result of this connection, there may be treatments in the future which utilize leptin in order to enhance the natural healing processes of bone tissue after breaks and fractures.

Leptin and the Brain

Although the primary trigger point for leptin is the hypothalamus, there are also receptors for the hormone at other locations within the brain. One of the largest receptor sites outside of the hypothalamus is the hippocampus.

Research has clearly shown that Leptin Deficiency has a negative impact on the normal function of neurons as well as brain proteins. In animal studies, normal neurological function in this instance can be restored by providing injections of leptin.

In humans, Leptin Deficiency is associated with neurological and cognitive changes that are associated with HIV, depression, and anorexia. There is even evidence in rats that leptin deficiency may play a role in Alzheimer's, and that providing leptin therapy may be able to increase cognitive ability and reduce the negative effects of the disease by limiting the concentrations of hyperphosphorylated tau and b-amyloid, which are two of the main factors which make Alzheimer's such a devastating neurological disorder.

Leptin and the Immune System

Leptin is intricately related to the immune system response of inflammation, and leptin has a regulatory effect upon a number of factors which affect immune health, including body fat, caloric restriction, stress, sleep, and Testosterone levels. It is hypothesized that the primary mechanism which links Leptin to immune health is that Leptin helps control the activity of cytokines released by adipose tissue.

Leptin is actually structurally similar to cytokines both in function and its molecular composition. There is evidence that Leptin plays an active role in the way that the body handles and manages stress, but the direct mechanisms are not completely understood. There is also a positive correlation between white blood cell count and leptin levels.

Diseases Associated with High Leptin Levels

There are a number of medical conditions which are associated with abnormally high leptin levels, especially those associated with inflammation. Among these are cardiovascular disease, chronic fatigue, and hypertension.

Elevated levels of leptin are correlated with overeating, the mass of adipose fat cells, and overall body composition, but leptin is not connected in any way to physical activity. Exercise does not stimulate or suppress the production of leptin directly. For this reason, it is hypothesized that leptin is designed to activate only with regard to inflammation related to adipose fat. Leptin promotes the formation of new blood vessels, promotes inflammation, and encourages cellular metabolism.

Based on these factors, it is believed that the elevation of leptin levels due to overeating is a mechanism designed to limit the stress on fat cells caused by abrupt changes related to increased caloric intake. When the fat cells no longer have enough room to absorb all the calories being delivered, this causes the body to begin to store fat in the muscles, arteries, and organs, which is dangerous.

So in this sense, leptin triggers satiation in order to prevent the body from eating so much that the fat cells can no longer make room for it all, but obesity causes the body to produce too much of the hormone, which can have negative effects. Like other inflammatory/stress hormones, the body needs leptin, but there are serious issues which can result when the hormone is allowed to remain at abnormally high levels for too long.

References:

The Facts on Leptin: FAQ - The Truth about the Hormone Leptin and Obesity

http://www.webmd.com/diet/features/the-facts-on-leptin-faq

Serum Leptin Levels in Males with Delayed Puberty during Short-Term Pulsatile GnRH Administration.

http://www.ncbi.nlm.nih.gov/pubmed/10090130

Wikipedia: Leptin

http://en.wikipedia.org/wiki/Leptin

19 August 2014

Enclomiphene Citrate Andropause Treatment Up for FDA Approval

Enclomiphene Citrate May Treat Andropause More Effectively than Bio-Identical Testosterone

Bio-Identical Testosterone has been used for decades in order to treat Low-T caused by Hypogonadism and Andropause. There is a drug currently undergoing Clinical Evaluation which is likely to reach the open market in just a matter of years, known as Enclomiphene Citrate.

Medications similar to Enclomiphene Citrate have long been used as fertility treatments for women, but studies indicate that the treatment can also provide men with a potent boost of Testosterone without a risk of overdose.

Enclomiphene Citrate Affects Men and Women Differently

In women, Enclomiphene Citrate encourages the process of ovulation, but in men, it encourages the release of precursor hormones which stimulate the production of both natural, endogenous Testosterone and sperm.

In fact, these trials provide evidence that Enclomiphene Citrate is even better than Testosterone Injections and Creams at restoring natural Testosterone Levels, all the while promoting healthier hormone balance and circulation in other ways.

How Does Testosterone Replacement Treat Low-T?

Bio-Identical Testosterone Therapy simply replaces the Testosterone that the body no longer produces at sufficient concentrations to sustain male health. Testosterone Therapy can bring Testosterone Levels back to normal, but it comes with side-effects, both inherent in the treatment and related to accidental overdose. Because Testosterone Therapy provides an outside source of Testosterone, the treatment suppresses the body's production of Testosterone Precursors that are responsible for healthy testicles, which leads to fertility issues as well as Testicular shrinkage.

Enclomiphene Citrate is Cheaper than Testosterone

Enclomiphene Citrate is also cheaper than Testosterone, meaning that, if the treatment is found to be effective and gains FDA Approval, and it appears likely that this will be the case, countless men will flock from Bio-Identical Testosterone to Enclomiphene Citrate in order to get more cost effective care that is easier to administer. Unlike Testosterone, which is generally delivered via injection or topical formulation, Enclomiphene Citrate is a simple pill.

Enclomiphene Citrate Clinical Research Study

At this point, Enclomiphene Citrate for Men is in the second stage of its clinical trial, after showing incredible promise in the initial stage of research. The details regarding this second phase will be published in the academic publication Fertility and Sterility.

Of course, the process for FDA Approval is a four stage process, but, based on off-label usage of similar medications, and the effectiveness of the treatment in the first two stages, it seems clear that Enclomiphene Citrate for Andropause and Male Infertility will almost certainly obtain FDA Approval.

Testosterone Deficiency Prevalent in American Society

Low-T, also known as Andropause or Age-Related Hypogonadism, is a prevalent condition among men in the United States. Millions of American males suffer from the condition, and studies suggest that the condition is still under-diagnosed, due to a number of different factors.

Testosterone Deficiency is most well-known for its impact on sexual health, but Low-T affects male health and longevity in a number of different ways. Aside from Low Libido, Infertility, and Erectile Dysfunction, other symptoms of Andropause include depression, anxiety, changes in body composition, loss of Bone Mineral Density, muscle atrophy, and lack of energy.

Low-T is a natural aspect of the process of aging, but not everything that is natural is healthy. Study after study shows that men with naturally high Testosterone tend to be both healthier and more well-adjusted than their peers that have lower levels of Testosterone.

When Does Testosterone Production Peak?

Biologically, our Testosterone Levels peak while we are in our teens and twenties, and start to fall off beginning in the thirties. Every man is impacted by Low-T in their own way, and some experience symptoms more quickly and more severely than others. Testosterone Deficiency is associated with a number of chronic medical conditions, from cardiovascular disease to diabetes to obesity.

The State of Modern Testosterone Therapy

One issue with Testosterone Deficiency as it is treated today is that there are no definite thresholds regarding how low Testosterone Concentrations must fall before a patient is ultimately diagnosed. This is partially because there is still ongoing research regarding Testosterone for Andropause, but also because each patient has his own personal genetic profile as well as their own set of unique lifestyle choices.

This means that part of diagnosing Low-T is up to the discretion of the prescribing physician, because it is up to his or her expertise to determine if the severity of the symptoms and the underlying hormone levels warrant therapy.

This also means that Testosterone Therapy is prescribed to meet our standards for what healthy Testosterone Levels should be, rather than the body's natural processes to provide youthful Testosterone. This is where Enclomiphene Citrate can be both useful and perhaps even superior to Testosterone Therapy for many patients.

Enclomiphene Citrate and Andropause

Andropause is a form of Secondary Hypogonadism, meaning that the testes are still fully capable of producing their own Testosterone, they just aren't receiving the same signals that they did when the patient was younger. Enclomiphene Citrate restores this youthful signaling, allowing the body to make just as much Testosterone as it needs to meet the needs of the body. Enclomiphene Citrate encourages youthful production of Testosterone, without the risk of overdose (or under-dose) that is sometimes associated with Testosterone Treatment.

Why is Enclomiphene Citrate Superior to Testosterone?

Bio-Identical Low-T Treatments restore Testosterone quite capably, but they do so without taking into account the other hormones and processes of the male body which depend upon Luteinizing Hormone, Follicle-Stimulating Hormone, and Gonadotropin-Releasing Hormone to take place.

When Bio-Identical Testosterone is administered, the body fully absorbs and utilizes the Testosterone, but the three precursors listed above, LH, FSH, and GnRH, no longer get produced in sufficient quantities. This condition does not have a significant impact on health and wellness, but it has a tremendous impact on both male fertility and the condition of the testes themselves.

Doctors Often Prescribe Testosterone to Men that Want Children

Many men take Testosterone without realizing the fertility risk associated with Standard Testosterone Therapy. This is because many general practitioners prescribe Testosterone for Low-T without fully recognizing the downsides associated with the treatment, and thus, they don't relay that information effectively to their patients.

Often, we think of Testosterone Treatment as a therapy for men in the latter stages of their life, but Age-Related Low-T can affect male health even as soon as the early thirties, and many men start taking Testosterone while they are still interested in having children, without recognizing the suppressive effect that the treatment has on a man's ability to produce sufficient sperm for conception.

This lack of knowledge on the part of many physicians is not anecdote, there are studies to back it up. A recent poll by the American Urological Association discovered that fully a quarter of urological specialists were not aware that Testosterone inhibited fertility, and would prescribe Bio-Identical Testosterone Treatments like Axiron to men that were vocally interested in having children in the near future.

Fertility Suppression Due to Low-T Treatment Temporary

Luckily, the fertility risks associated with Bio-Identical Testosterone are short-term, and fertility returns to pre-treatment levels after therapy is suspended, but this still means that many men that would greatly benefit from Testosterone Therapy don't get the opportunity for treatment because of their desire for children.

Clomid vs. Enclomiphene Citrate

In the very near future, there will be a new option available for these men, so they can protect their health and their sexual function while also promoting the healthy production of sperm. Enclomiphene Citrate is a component of a medical treatment that has long been on the market in generic form known as Clomiphene Citrate.

This treatment is also available under the brand name Clomid. The treatment was originally designed to improve fertility in women, but also shows some effectiveness at restoring Testosterone Levels in males. In women, Clomid and Enclomiphene encourage the production of female sex hormones, but in men, the medical treatments encourage the production of Testosterone and sperm.

Clomid is a combination of two active compounds, Enclomiphene Citrate and Zuclomiphene. The benefits of Clomid on Male Sexual Health are primarily the result of the Enclomiphene component of the medication.

The issue with Off-Label prescription of Clomid is that Zuclomiphene does increase the level of Estrogen in the body by a slight amount, meaning that the ideal form of the medication would omit Zuclomiphene entirely. Because of the Estrogenic effects of Zuclomiphene, Clomid is often prescribed in combination with Arimadex in order to counteract those effects and optimize treatment.

Enclomiphene Shown to Be Effective in Stage-2 FDA Trial

In the second stage of clinical research for Enclomiphene Citrate, medical specialists from the Houston campus of the Baylor College of Medicine and Repros Therapeutrics provided 73 male patients with Enclomiphene Citrate for the treatment of Low-T caused by inhibited stimulation of the testes. This is most commonly the result of natural aging, but there are other factors which can impede the release of precursors from the pituitary and hypothalamus as well.

The study went according to the hypotheses supported by Off-Label use of the medication. The researchers found that Enclomiphene Citrate was incredibly effective at increasing Free and Total Testosterone to youthful levels, as well as LH and FSH Levels, which are necessary for proper sexual function.

As a result, Enclomiphene Citrate had no inhibitive effect upon the production of sperm, and perhaps even improved fertility among patients, though this is unclear.

Enclomiphene Works Better Than Clomid for Men

The lead researcher of the study, Dr. Ron Wiehle, explains that Enclomiphene Citrate works via the same mechanism as Clomid, which is prescribed Off-Label, but appears to do so with improved consistency. Further research could prove or disprove that notion, but because Clomid is no longer under patent, there is no financial incentive to study its effects.

On the other hand, Enclomiphene Citrate is still under patent, and is potentially effective for a greater subset of the male population, which provides the motivation for funding and research by private pharmaceutical manufacturers such as Repros Therapeutrics.

Enclomiphene Slightly Reduces IGF-1 Levels

Prior research shows that Enclomiphene Citrate does have a slight suppressive effect upon IGF-1 Production in men. This means that Enclomiphene is likely not a good option for men that simulataneously suffer from significant HGH Deficiency and Testosterone Deficiency simultaneously. This does mean, however, that Enclomiphene Citrate is safer for the prostate than Testosterone Therapy. Further study is needed to elucidate the impact of Enclomiphene upon IGF-1.

Enclomiphene to Be Marketed as Androxal

Although Enclomiphene Citrate is not available on the open market quite yet, the plans are to sell and distribute the medication under the brand name Androxal. Androxal will be specially formulated for male use, to provide the optimal amount of medication to restore the youthful cascade of male hormones necessary to restore vitality and sexual potency.

One reason why there is so much interest in Enclomiphene Citrate is that men in America are choosing to have children later and later in the lifespan, meaning that the segment of the population that experiences symptoms related to Low-T while also being interested in having children continues to grow.

Interested in Enclomiphene Now? Talk to Your Doctor About Clomid!

Although Enclomiphene Citrate is not currently on the market, you can still talk to your doctor about Clomid (Clomiphene Citrate), and find out if you are a candidate for treatment. Clomid is designed and certified for use by women, but there are many physicians all across the country that are highly experienced with the treatment regimen. Clomid may never gain enough traction for FDA-Approval, but the treatment has been used effectively for decades.

28 September 2015

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If your doctor only prescribes testosterone by itself, you will probably have a rough ride. The tendency is for you to feel great the first couple months, while you increase testosterone levels, followed by a slow deterioration, once your estrogen creeps up.

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L-carnitine: Improves Cognitive Function In CentenariansL-Carnitine: Improves Cognitive Function in Centenarians
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Flax Seed Oil: Longevity And Anti-aging MedicineFlax Seed Oil: Longevity and Anti-Aging Medicine
Knowing Two Languages Can Postpone DementiaKnowing two languages can postpone dementia
Mind, Not Matter, Rules, Leading Thinker SaysMind Not Matter Rules Leading Thinker Says
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