Ghrelin

 

Ghrelin is mostly known as the hunger hormone, but it has many more functions than this alone.

Ghrelin is a peptide hormone primarily produced by the stomach. Ghrelin is secreted by the stomach when it is empty and increases your appetite, sending a message to your brain that you need to eat. This message is sent through your bloodstream or signals via the vagus nerve to your brain.

It has been said that too much ghrelin makes your body crave fatty and sugary foods. In saying this, Dr. Mauro Di Pasquale, mentions a study where low carb, high fat intake reduced ghrelin levels, and as such decreased appetite and fat formation. He says that this is one of the ways that the body limits fat formation on a high fat diet.

Things that can increase ghrelin levels include:

·       Lack of sleep

·       Fasting

·       Chronic stress

Ghrelin signaling increases food intake, fat storage, and reduces thermogenesis and reduces energy expenditure. So, you want to control ghrelin levels as much as possible if on a fat loss diet or even to maintain your current body weight.  

How can you control ghrelin levels? Get enough sleep, ensure optimal amounts of protein, increase muscle mass, avoid excess sugar, eat regular meals / don’t fast for too long, and use refeed meals strategically. Refeed meals will ensure you aren’t low calorie for too long and will help increase leptin levels.

The major biological functions of ghrelin include:

·       the secretion of growth hormone,

·       the stimulation of appetite and food intake,

·       the modulation of gastric acid secretion and motility,

·       and the modulation of the endocrine and exocrine pancreatic secretions.

Ghrelin also exerts wide physiological actions throughout the body including: inflammatory functions, glucose homeostasis, reproductive functions, cardiovascular function, and bone formation.

The clinical applications of ghrelin have been investigated in both eating disorders and muscle wasting conditions, including obesity, anorexia, cachexia, and sarcopenia (muscle wasting due to aging).

“Ghrelin can indirectly increase muscle mass by increasing food intake and activating the GH/Insulin-like growth factor-1 (IGF-1) axis in cachexic mice”.

Ghrelin has multiple beneficial effects on cardiovascular functions, thereby improving cardiovascular disease risk. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. “Overall, ghrelin treatment may reduce cardiac sympathetic nerve activity (CSNA) inflammation and oxidative stress in the heart, and induce angiogenesis. More studies are needed to further assess whether ghrelin is beneficial for treating heart diseases.” They are looking into the usefulness of ghrelin analogues to find out more about any potential benefits.

Ghrelin exerts many anti-inflammatory actions in inflammatory bowel disease, pancreatitis, sepsis, arthritis, and diabetic nephropathy.

“Several synthetic ghrelin mimetics are being pursued in clinical trials for diverse indications. Three compounds are currently in development. Macimorelin is in clinical trials for the diagnosis of GH deficiency. A second compound, anamorelin, is in clinical trials for the treatment of cancer cachexia. A third compound, relamorelin (also known as RM-131) is currently in phase II clinical trials and is being developed for treatment of diabetic gastroparesis and other gastrointestinal (GI) disorders.”

A concern with ghrelin though is its link to cancer development and progression. “Ghrelin and GHS-R have been detected in many endocrine and non-endocrine tumors (21, 22), suggesting that the ghrelin/GHS-R axis might be associated with tumor growth and progression. In pituitary tumors, ghrelin mRNA is detected in non-functional adenomas, GH- and gonadotropin-producing adenomas and prolactinomas, with highest GHS-R expression detected in the GH-producing adenomas”. It has also been linked with breast cancer as well.

 

 

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863518/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819073/

Amino acids and proteins for the athlete – Dr. Mauro Di Pasquale

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049314/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895712/

 

Leptin

Leptin is a hormone made by fat tissue that is involved in appetite control. Leptin lets the brain know how much fat you are storing. When leptin levels go up, your appetite goes down. It let’s you know when you have had enough to eat. Leptin also speeds up your metabolism.

This is when everything is working well and you are lean. Most overweight and obese people actually produce too much leptin. They become what has been termed, leptin resistant.

Leptin resistance is very much the same as insulin resistance. When a person becomes leptin resistant, it takes more and more leptin to tell their brain that they are satisfied and to stop eating. Because leptin is made from fat cells, they have to make more fat to produce enough leptin to finally get the message across to the brain to stop being hungry and to stop producing fat. This creates a vicious cycle.

Foods that trigger surges in leptin production can feed into this vicious cycle. They tend to be carbohydrates such as breads, pastas, grains, cereals, and starchy vegetables. These carbohydrates can increase leptin levels for 4 to 9 hours post meal.

Another problem with leptin, as Dr. James Lavalle explains, is that it is a source of inflammatory compounds in the body such as aromatase, IL-6, TNF alpha, estrogen, cortisol, and angiotensinogen, and enzyme that contributes to hypertension.

On top of this, Dr. William Davis has said that leptin has demonstrated direct joint destructive effects. The more overweight the individual, the more leptin within the joint fluid, and the greater the severity of cartilage and joint damage.

For people to lose weight, lower inflammation, and improve their health in general, it is important for them to restore leptin sensitivity so that leptin can do its job of turning off hunger.

To restore leptin sensitivity, you can limit the amount of carbohydrates that spike leptin levels rapidly and eat more good fats, which don’t have much of an impact on leptin levels.

In the book, The Perfect Health Diet, the authors explain that leptin follows a strong circadian rhythm. Leptin levels are lower of a morning and increase over the course of the day, peaking in the middle of the night. To enhance leptin rhythm, they suggest we should eat most of our carbs around sunset.

When it comes to dieting and maintaining leptin levels, it only really matters once you are lean. If you are 40% body fat and go down to 20%, you still have plenty of leptin left in the fat cells. It is important not to confuse hunger with leptin being low. For most people, they need to diet for 3-4 weeks before starting to think about a re-feed meal. If fatter, it could be even longer.

Once you are lean, then this is where the re-feed serves its purpose in trying to avoid a decrease in leptin levels. Re-feed with clean carbs or clean fats. It is the increase in caloric intake that helps prevent the leptin from crashing.

References:

The Rosedale Diet – Ron Rosedale

Cracking the Metabolic Code – James B. Lavalle

Wheat Belly – William Davis

Christian Thibadeau – Program design seminar

The Perfect Health Diet – Paul Jaminet, Shou-Ching Jaminet