Introduction

Some uses of peptides today are reviewed.

 

Disclaimers

This is for the purpose of education only. Don’t try to self supplement or self medicate.

 

Discussion

Peptides are usually 20 to 50 amino acids long, connected by peptide bonds. Anything longer they’re considered polypeptides. Above 100 is a protein. So, as these are all strands of amino acids, all of these will have an amino group on one side, and a carboxyl group on the other. So, most peptides are so small, that just about any route of administration is extremely effective, oral, sub Q, and many new routes of administration put them at a clear advantage over drugs for general use.
 
Peptides are in all cells. All peptides are synthesized by ribosomes. Processes of transcription and translation and messenger RNA will not be discussed here. But the take-home is, they are natural! The body makes them.
 
All of these different types of peptides can be enzymes, ligands, hormones, cell receptors themselves, just about anything! And, since they have this receptor relationship, things can be attached to them, and they can attached himself to receptors with or without other things attached to them.
 
Hence, limitless uses beyond up regulating growth hormone.
 
Another discussion elsewhere in this blog, “Growth Hormone and Peptides,” reviews general principles of peptides in their up regulation of the body‘s production of growth hormone. Check that out please.
 
Listed elsewhere in other discussions in this blog detail the specific benefits of peptides currently in use. Brain, muscle, gut… Check those out, too.
 
Aging or disease (autoimmune, insulin resistance, cancer) is the decrease of GH, decreases of IGF-1, leading to sarcopenia, osteopenia, decreases in insulin sensitivity, dysfunction of amino acid uptake, loss of cognitive function and memory, decrease immune system, decreased mitochondrial biogenesis and thus efficiency of the cell, thus inability to utilize substrates appropriately – again, ALL from BOTH disease or aging.
 
So, when someone says “peptides,” it’s mostly about the up regulating of GH to help the body using naturally occurring peptides. But some peptides are used simply because of the specificity of the receptors guiding them conjugated with things towards tissues of interest. And some are even used for downloading transcription and translation to alter cell functions.
 
Over 7000 naturally occurring peptides have been found. They must be doing useful things otherwise the body wouldn’t have them. They are under much review. So, discovering them isn’t an issue. We just have to keep finding them, and discovering their uses. Hundreds of active investigations and proposed investigations are on deck at this time.
 
There are 60 peptides currently approved by the FDA. Although most of the research is for metabolic disorders and cancer, there are exciting other uses already allowed. A few are reviewed here.
 
Basically, if you supplement peptides that are naturally occurring that operate to up regulate GH naturally or, alternatively, simply up regulate the body‘s production of the peptides that up regulate GH naturally by using synthetic peptides that are not naturally occurring, you achieve desire benefits safely.
 
Or, simply based on the specificity of peptide binding to cells, outside the realm of GH up regulating, you can use peptides that you know will specifically bind to cells to bring things to those cells to do things to those specific cells, like killing cells that are cancer cells.
 
In general, most of these peptides that are supplemented are poorly absorbed orally, so must be injected by the patients. Some are intranasal.
 
GH and IGF-1, please keep in mind, are made both centrally in the brain to regulate GH release, and peripherally in the tissues, at a local level. Peptides that up regulate them have those been shown to have a wide variety of functions and thus uses.
 
Gut
 
BPC is made by the gastric mucosa. So similar versions of it can be synthesized like BPC-157. This particular synthetic peptide is showing promise in angiogenesis and other regeneration especially if tissue damage has occurred. BPC is oral, injectable, and some are trying to use it intranasally.
 
Brain
 
The brain is a great example of one tissue type where GH up-regulating helps us.
 
Neuroplasticity is a very real world. And, consistent with the general theme exemplified by muscles requiring exercise, the brain is not going to improve by just receiving peptides. The brain must be challenged. And then receive peptides.
 
And it’s the same general theme as is the case for all tissues: if the tissue loses its ability to respond to stress, disease and aging follows. Similarly, if the brain is not challenged, it loses its ability to respond to stress, and disorders and age induced inflammation follow. And neuroplasticity is lost.
 
Peptides are giving that diseased or aging cell a chance to respond to challenge back.
 
GHRHs and GHRPs are growth hormone releasing hormones and growth hormone releasing peptides, respectively, that the brain, specifically the hypothalamus, produce, that obviously up regulate growth hormone. And the synthetic mimics that we can make last a little longer and then actually occurring ones do.
 
“Fluid intelligence,” which includes short term memory, is actively degrading overtime. It is affected by GH and IGF-1.
 
Well established is the fact that GH influences memory. So if we up regulate it, we improve memory. And this has been confirmed. The pathways even are being elucidated. Brain cells like all the other cells in the body have receptors for GH. The GH binds to the cells, and this leads to the cell’s production of IGF-1 and IGF-1 allows the cells to solidify a memory; and consolidate it. Downstream from this as well, it leads to the cell’s increased ability to produce IGF-2, which also leads to improve memory (hippocampus).
 
And research on GH receptors in the brain shows that GH up regulation by peptides optimizes neural plasticity.
 
Every cell in the body has the capability of making its own cortisol. In brain cells that make their own cortisol in response to stress from cortisone using the enzyme 11-beta-OH-dehydrogenase, GH inhibits that enzyme! And the coenzyme 6-hexose-dehydrogenase is affected by IGF-1. Hence, two ways of limiting the cell’s ability to produce too much cortisol.
 
But remember, as exercise is to increasing muscle strength and size, and as intermittent fasting is to increasing metabolic efficiency and health, an oxidative stress is also required for peptides to benefit neurons. A stressor is always required to challenge a tissue if it is to benefit from growth hormone up regulating.
 
The brain releases different forms of growth hormone released by somatotrophs in the brain to deal with different conditions. There are different forms of IGF-1 that are specific to different requirements of the genome to respond to different stressors. Peptides available to up regulate growth hormone in the brain simply tell the brain to up regulate the growth hormone. The brain decides which type is needed!
 
 
Diabetes
 
GLP-1’s and GLP-1 agonists… There are peptides being formulated from these that can be dosed weekly for diabetics without ever leading to hypoglycemic events.
 
GH in general increases glucose uptake, thereby increasing glucose tolerance, reducing insulin resistance.
 
But even more specifically, a peptide has been discovered in the mitochondria called MOTC-S that, in response to stress, goes to tell the nucleus that it needs certain transcription factors to produce certain needed proteins to change the cell’s situation in order to live/avoid apoptosis/utilize substrates better. This peptide can change and reverse diabetes in a pancreatic beta cell.
 
Muscle
 
GH can improve function in the muscle.
 
GH can improve muscle mass.
 
And the general theme of necessary oxidative stressor for peptides to work applies of course to the muscle. When it comes to muscle, that oxidative stress or is of course exercise. Any cell that is to benefit from peptides to optimize itself needs stressors.
 
My patients are starting to ask me more about peptides. When I describe how they will help their muscle, they ponder on then say, “I’m just going to do it the old-fashioned way and go to the gym.“ Absolutely they have to go to the gym! Whether they use peptides or not! The gym is the necessary stressor for peptides to work.
 
The cell must be constantly challenged if it is to constantly up regulated.
 
  1. Stress the muscle
(Challenge it with exercise)
More mitochondria utilization
More mitochondria
More/better use of fatty acids
(Oxidative phosphorylation)
  1. Muscle hypertrophies
 
Not:
Peptides given to muscle just sitting around causes hypertrophy? No.
 
Exactly how this happens at a biochemical level has been elucidated.
 
GH promotes the muscle cell mitochondrion oxidative capacity by significantly influencing the transcription of genes.
 
Basically, PGC 1 alpha is the power behind the up regulation of a cell – in any cell, including any muscle cell. The only way we can effectuate this up regulation of this amazing cellular machinery common to all muscle cells, PGC 1 alpha must be phosphorylated in the nucleus to do its job – and that’s usually done by AMPK. AMPK is up regulated when you fast. AMPK is up regulated when you exercise.
 
And what is PGC 1 alpha’s job? It up regulates T-Pam, a transcription factor for making mitochondria! More mitochondria is ALWAYS good. More factories for making more energy? Oh yeah. That’s good.
 
In summary, things like exercise or intermittent fasting lead to up regulation of AMPK, AMPK phosphorylates PGC 1 alpha, PGC 1 alpha up regulates T-Pam to make more mitochondria, obviously leading to the up regulation of cellular machinery efficiency.
 
The 1000 foot point of view summary of this: exercise and intermittent fasting lead to the biogenesis of mitochondria.
 
This in turn alters muscle type fibers to a type of muscle type fiber that uses more mitochondria. Ask any athlete the significance of this. This allows that muscle fiber to use more oxygen… To make more ATP. Bam.
 
Also, PGC 1 alpha has a role in increasing anti-oxidants. PGC 1 alpha must combine (in the nucleus) with nuclear factor 2 to make the antioxidant system work in the nucleus.
 
The electron transport chain (which generates our energy) is made of cytochromes… Cytochromes are made by the nucleus and cytochromes made by the mitochondria. The mitochondria tweaks it’s cytochrome production. The nucleus tweaks its own cytochrome production, separately. The interplay creates a balance depending on whether the cell wants to focus on function – energy usage – or energy production. This interplay is how the cell controls oxidative stress. GH up regulates both sides of this.
 
As muscle is essentially the largest endocrine organ in the body, this gives me a nice segue to…
 
Insulin Resistance
 
Decreasing resistance to insulin is at the root of reducing the morbidity of every disease group including diabetes, cancer, and autoimmune disorders. That’s pretty much everything folks. And up regulating GH does this.
 
Yes, up regulating GH in essentially every cell of the body leads to increased glucose uptake. This is one in the same as decreasing resistance to insulin.
 
The transcription of increasing Sellier mechanisms leading to increased glucose uptake are guided by up regulating GH.
 
I segued from muscle uses to decreasing insulin resistance. Let me explain. Muscle is indeed the largest endocrine organ in the body. That is, it contains the largest amount of amino acids. Thus, all the cells of the body can go to muscle to get amino acids when they need them. But this must be done by signaling. And this signaling is done by peptides called cytokines.
 
There are over 500 types of signaling cytokines and chemokines signaling cellular changes from the muscle. Muscle after all is pool of amino acids to the brain, the kidney, and the liver. And the cells of all of these tissues are going to go to the muscle to get amino acids when they are in demand – coordinated by a conversation that uses cytokines.
 
Thus, muscle must be constantly repleted of its amino acids. GH is key to promoting this.
 
GH is essential to these processes, both at the taking of amino acids from muscle, and at the requesting of amino acids from all of the bodies tissues.
 
Sarcopenia, a big problem in aging, can be nicely controlled with peptides that up regulate our bodies GH.
 
Liver
 
GH can improve function in the liver.
 
Kidneys
 
GH influences the podocytes, cells that line the kidney tubules.
 
Adipose tissue
 
GH can improve function in fat tissue.
 
GH can produce shifts in body composition.
 
Decrease in fat in general is healthier, yes.
 
Beige that is more healthy than white fat tissue. We want more beige because it has more mitochondria in it, and that is always good. Beige add a post tissue is more thermogenic… It’s more efficient. Remember, more mitochondria is always better. More power houses, factories in the cell.
 
GH it turns out converts white to beige adipose tissue. Bam.
 
Cardiovascular
 
GH can improve cardiovascular capacity. GH can improve exercise tolerance. GH can improve endurance.
 
GH, in its ability to influence IGF-1, stimulates nitric oxide synthesis, the critical substance of course for angiogenesis.
 
GH has an effect on homocysteine levels, fibrinogen, cystine levels.
 
GH can affect lipid metabolism to reduce cholesterol, the stickiest large molecule in the blood given blame for so much in the world of cardiac and cerebral vascular ischemic events.
 
Bone
 
GH can improve function in the bone. GH can improve bone density. Thus, GH is important in osteoporosis and maintaining bone integrity and function.
 
Osteopenia, a big problem in aging, can be nice to controlled with peptides that up regulate our bodies GH.
 
Sleep
 
GH can improve sleep. Stages of sleep. Sleep cycles. The most important release of growth hormone is at night. The first phase in the cycle of going to deep sleep, phase 4, is where the most GH is secreted by the brain.
 
With aging, we lose phase 4. So we lose much of our GH.
 
Understandably, GH, a proliferator, allows the body to repair best at night.
 
Immune system
 
GH is an up regulating agent. Immune cells, B and T cells, produce their own GH. As a result, they can up regulate more immune cells.
 
GH is also a signaling agent. Because immune cells, B and T cells, produce their own IGF-1 and GH, they can respond to and create their own hormones that function at both paracrine and endocrine levels.
 
GH can definitely improve the immune system. This is well documented because when there is a decrease in GH in the bloodstream, we see thymic medulla involution. And thymopoesis (the body‘s production of T cells) is shown to be lost. Also well documented, the administration of GH can restore the thymus to health in a mild regenerative capacity, or at least cap further decrease in its function – so at least protective.
 
Similarly, the up regulation of certain cytokines and interleukins has been documented by supplementing GH.
 
So if the immune system is up regulated, it has an auto regulatory, self perpetuating ability to continue that up regulating subsequently on its own. Clinically, these patients may not need much maintenance once up regulation is launched.
 
Regeneration (Stem Cells)
 
And one of the most exciting new uses of peptides and GH up regulation is with regeneration, specifically with stem cells.
 
GH optimizes stem cell health.
 
IGF-1 up regulates neurogenesis in the adult brain – well documented. Even small doses of it can trigger the differentiation of regenerative cells like stem cells and their progeny, the progenitor cells.
 
Over time, as we age, there is a well documented decrease an expression of IGF-1 necessary for neurogenesis in the brain, especially the hippocampus. Neuroplasticity is lost as we age. GH and IGF-1 can give this back.
 
Stem cells, the regenerative cells in our body, we now know are in all tissues. They have different names in different tissues, satellite cells in the muscle, pericytes along all endothelium, and so forth. But they are all stem cells and they are everywhere, ever ready for the main 3Rs, repair, rebuild, regenerate. Well, all stem cells have GH receptors, and they all have GHRH receptors. Turns out these receptors need to be stimulated for a stem cell to remain able to go into action at any time.
 
Stem cells must remain in a “quiescent” phase to be able to go into action.
 
Stem cells in “senescence”, a zombie like state any cell can get into in which it neither functions normally nor concedes to die, cannot be called into action. Any cell in senescence can’t continue its cell life cycle, halting after it stops doing any functions to help tissue in anyway, but short of death (apoptosis).
 
Inflammation leads to senescence. Senescent cells are cleared by stem cells, one of their many exciting functions being elucidated at this time. But a stem cell in senescence? No good.
 
We want our stem cells in quiescence in order for them to be able to function.
 
Turns out it’s the correct ratio of NAD+ to NADH that makes stem cells stay in the quiescent state! Up regulating GH systemically produces this correct NAD+ to NADH ratio.
 
Vasopressin
 
… Is a peptide.
 
Gonadotropin releasing factor
 
Is another peptide…
 
Oxytocin
 
Another peptide…
 
Cancer
 
You can attach a peptide that you know will attach to a tumor cell to a virus that oncologists know kill a tumor and, and thereby introduce the conjugated virus and peptide to a cell specifically enough to accurately kill cancer cells.
 
Weight loss
 
Probably the most common effect, desired and otherwise from the use of GHRP is weight loss. This is as a result of the up regulation of oxidative phosphorylation (of fat) produced by GH. This up regulates mitochondrial function and thus the production of ATP.
 
 
Physiology
 
And how is all of this increased efficiency, correlated with weight loss usually, consistent with a healthier state, you ask?
 
Better put, how does up regulating oxidative phosphorylation by using a better substrate, fat, actually lead to the increased transcription of more efficient and thus healthier cellular enzymes and machinery?

Conclusion

GH receptors are essentially everywhere, muscle, immune cells, kidney, pancreas, so not just the brain.
 
As such, GH can act as an up regulating hormone. And it can also act as a signaling agent.
 
So, as long as we are up regulating our body’s production of GH instead of supplementing it exogenously, there are limitless uses for this. And complete safety, in general. There’s no toxic, completely foreign feel to peptides because they are not really foreign to our cellular culture.
 
GH has an anabolic effect. It up regulates protein synthesis, it up regulates glucose uptake. Hence, cell growth, differentiation, ATP production. But perhaps most importantly above all, it gives the cell the most effective substrate for metabolism, fatty acids. Hence, probably the biggest use we hear for GHRP is weight loss.
 
In summary, if you can make a self more efficient by using a better substrate, fat, you improve metabolism, health, and longevity in general because you have improved the efficiency of the cell, thus optimizing its physiology.
 
Furthermore, in the most current literature, we are seeing a protective nature to many of these GH augmenting peptides. They actually protect our cells from stressors and disease every day before stress and disease happen.
 
In overview, peptides that up regulate the body‘s production of GH not only help with proliferation, differentiation, and hence regeneration, because they help with cellular metabolism at almost every little step, they are anti-aging.
 
Thus, GHRF and GHRH and any peptides that up regulate the bodies GH, at the end of the day, can lower drugs required for most of these groups. All of these peptides are those synergistic with other conventional care – drugs that have so many side effects.
 
Even hormone replacement (HRT) therapy which helps so many patients can be reduced by using peptides. Yes, peptides that up regulate GHR synergistic with HRT. This has even been well elucidated. The first step that converts cholesterol toward steroids is the conversion to pregnenalone.
 
My point… Bottom line, since peptides helps cellular efficiency at every metabolic step, they help return the body from a disease state to a homeostatic state in almost every capacity that you can imagine. And – some speculation here in theory still, but it’s generally accepted – because aging means that we have an over holding back by somatostatin, to help the aged cells which are still capable of doing everything a teenager can do, we can up regulate GH to return to a state of youth.
 
GHRP. Peptides that up regulate growth hormone.
 
GHRH. Hormones that up regulate GH.
 
Let’s learn all about these and fine-tune what we can do to help a six-year-old do with a 20-year-old can do.
 
Our capacity? Our pituitary could do what that of a 20-year-old could do until we turn 150 years of age.
 
We can turn around sarcopoenia and osteopenia – end products of unattended aging. We can turn them around. We can turn around aging. Protein is required. Let’s specify the type and make the correct type of peptide decisions to replenish.
 
Disease states in which you are losing protein? Give the protein back, and we can turn it around… With the correct peptides. To increase GH.
 
Or help the body make its own GH up regulating peptides. Get it the right type of amino acids. Improve amino acid uptake.
 
Mitochondriogenesis follows. Improved energy efficiency follows that. Reduced disease and or reduced aging follows that.
 
And again, the youthful every through our pulsing of GH that a teenager can do that we start losing in our 20s is something we can get back.
 
GHRH’s and GHRP’s can retrain somatotropes to pulse.
 
Let’s turn the machinery of aging around. Let’s turn the machinery of diseased tissue around. Let’s improve amino acid uptake. Let’s do this by up regulating GH. Let’s do this by using GH up regulating peptides.
 
And big general principle: stressors up regulate health. So caloric restriction is a stress on the muscle, so that’s going to strengthen muscle. Exercise is a stress on the muscle, so that’s going to strengthen the muscle.
 
We can mimic what exercise and caloric restriction do using growth hormone enhancing peptides, yes. But we must also exercise and practice intermittent fasting so that the peptides that we are supplementing are helping a stressed muscle become stronger. Otherwise, a muscle just sitting there getting peptides is not going to be stressed and thus won’t get stronger.
 
In disease as well as in aging, what goes wrong is oxidative phosphorylation and the like – cellular machinery for making energy – what is called oxidative stress. We now know we can restore those pathways to youthful if the oxidative stress is functional like exercise and intermittent fasting by using peptides that up regulate GH which is anabolic. We now know we can regenerate those pathways with peptides that up regulate GH production if the oxidative stress has been severe enough to damage them as is the case with disease.
 
So if the answer to a problem of aging or disease is a return to normal physiology, let’s do it the way the body does it, using peptides natural to the body.
 

Stay well,

DAVID ALLINGHAM, M.D., MS

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