The basics that will allow you to understand this latest hot topic are presented.
This discussion of the interaction of peptides and your bodies growth hormone levels is for the purpose of education only. Don’t try to self treat yourself.
Most of us are aware that the body makes growth hormone (GH; also known as somatotropin). It is made by the pituitary gland, and it has many beneficial effects for the body. Growth hormone releasing hormone (GHRH) is secreted by the hypothalamus, goes to the pituitary somatotrophs, where it triggers their release of GH.
Cells have receptors for GH. When the GH binds to the cell, it directs the cell’s protein production, both nuclear and mitochondrial DNA transcription and all those pathways (normal physiology includes the up regulation of beta oxidation, the up regulation of oxidative phosphorylation from the electron transport chain, the up regulation of the Kreb’s cycle production of ATP, and the up regulation of anti-oxidant production), producing healthy proliferation and thus terrific anti-aging effects.
Yes, every cell has two genomes, the nuclear genome and the mitochondrial genome, working in concert together to keep the cell healthy. If there is a stressor on that cell, trauma, disease, substrate abuse, the mitochondrial genome falls into disarray and is unable to handle substrate (glucose, fat) correctly. Glucose intolerance occurs. Insulin resistance occurs. Disease advances.
Up regulating GH in the body it turns out is extremely healthy. It clearly restores mitochondrial energy creating efficiency in a diseased cell. But it also optimizes it in the seemingly healthy cell that has fallen behind due to the more subtle stressors that have come with age – gravity, exposure, regular wear and tear even.
However, if GH is supplemented (and that’s illegal in the US for good reasons that I’ll explain here), it bypasses the body’s feedback mechanisms and can thus inhibit the body‘s natural ability to make GH, and lead to unhealthy situations.
So, we stick to the healthy harnessing of increased GH in the body by studying how the body increases GH naturally. And by doing this, we have discovered a lot of things that will increase the body’s ability to increase its own GH, and most of those are allowed. It’s called up-regulating GH, and if done with the guidance of a trained physician, it can lead to great results.
Exercise and intermittent fasting are two spectacular things that increase the body’s ability to make its own GH, and are both great anti-aging things to do. We knew that. And that’s why.
But there are also substances that safely up regulate GH while not hurting the GH feedback loop, because no exogenous GH has been supplemented. They are classified into two main groups, growth hormone releasing peptides and growth hormone releasing hormones.
For an understanding of how these work, you have to understand the basic physiology of GH release.
Turns out that (like most hormones) GH is pulsed all day at a rate that is very patient specific… Anywhere from once to six times a day. Release, recover. Release, recover. Usually a three hour window before it’s potential for release is once again allowed. All governed by GHRH pulses. Meanwhile, simultaneously, there is a constant inhibitory signal from somatostatin on the somatotrophs preventing GH release. Somatostatin has to allow GH release. The every three hours window as stated – the somatotrophs have the potential to release GH.
GH releasing peptides (GHRP’s) up regulate GH release in a different way from GH releasing hormones (GHRH’s).
GHRH’s up the machinery for improved GH release. GHRP’s inhibit somatostatin to allow GH release.
We can supplement GHRH’s, multiple are federally approved and on the market (Sermorelin, modified CJC12195…). We can supplement GHRP’s (modified 129, others) – multiple are federally approved and on the market.
So you get it. GH that the body makes has beneficial effects. If increased, we can better those effects. Can we do more than exercise and intermittent fasting to up regulate our bodies on production of endogenous GH? Yes.
Our bodies produce less and less GH as we age. But the body, the cell, of a 90-year-old still has the exact same potential to produce the GH as that of a young adult! We just have to turn that cell on.
With the peptides that up regulate GH, so, with GH, we are trying to up regulate/return the body back to a physiologic state. We are not going for supra-physiologic status.
We are trying to get the cell into a homeostatic pattern of living. This is not homeopathic medicine. Please keep those two terms distinctly separate and unequal.
And this resetting of cellular state we hope will be somewhat permanent in its ability to better handle substrates, glucose, fat, until it falls into disarray again.
It’s a return to cellular efficiency – with regards to handling substrates above all – for as long as possible, per tuneup. This up regulating of substrate handling capacity occurs of course in the mitochondria.
The cell had fallen into a state of disarray and poor mitochondrial function due to some stressor. So the GH upping peptide fix may not be permanent, assuming another stressor may come along.
And one of the beauties of all this is that these peptides don’t have to be devised or invented like drugs or artificial manipulations that have fascinated big Pharma for decades. They just have to be found. Correct. Right here. In our own bodies. And they are indeed all found in the body. We are simply looking to see what the body does to make its own GH.
How GH Produces Benefits
GH produces its benefits by increasing insulin like growth factor one (IGF-1).
Briefly, cells have GH receptors. Some cells have GHRH receptors and GHRP receptors on the same cell. Many cells have IGF-1 receptors (IGF-1 is mainly made by certain cells that are up regulated by GH).
GH, in general, binds to a cell and improves cell function, makes cells take in glucose, etc. (note: increasing glucose tolerance, decreasing insulin resistance!), and increases cell proliferation. And GH increases IGF-1.
IGF-1 is a protein hormone that provides the negative feedback mechanism to GH.
IGF-1 also leads to up-regulating of cell activity, also leads to an increase in growth and proliferation like GH, but there is also differentiation that occurs with IGF-1.
And IGF-1 is also about cell survival.
Since IGF-1 is about differentiation and cell survival, IGF-1 does things to protect cells from apoptosis.
There are anti-apoptotic proteins and pro-apoptotic proteins. The mitochondria, powerhouses of the cell, decide whether or not the cell is going to go into apoptosis or not. Mitochondria contain the DNA to produce the proteins that govern this. There are anti-apoptotic proteins and pro-apoptotic proteins it turns out that work in a see-saw relation deciding for or against apoptosis, depending on the balance they are shifted.
But there’s two more requirements that makes this whole system really work. One, there must be a stressor. In the case of muscles, it’s exercise. Brain: using it. Like that. It’s an ongoing oxidative stressor that the tissue requires to grow or maintain youth or undo damage so you’re not just firing peptides at it. Two, the stressor must be pulsatile. Again, using muscles as an example, if you were to exercise every day without recovery, the cell machinery’s receptors are going to become refractory to the peptide signal. The recovery allows the muscle a chance to rest. Without recovery, it’s going to break down. And that’s only part of the disease or inflammatory aging problem.
Harmful effects of excess GH come from excessive exogenous GH inhibiting the body’s own production of its own GH. So exogenous GH is understandably illegal – unless a person has a condition reducing their body’s ability to respond to GH (AIDS patients on anti-retroviral drugs that have this effect on GH metabolism) or a person has a condition in which GH is not manufactured correctly (GH deficiency or GHD).
Harmful effects of excessive GH up-regulating come from excessive receptor stimulation, leading to receptor shut down. Not a good condition either. So as GH up-regulation using peptides is completely legal, it should only be conducted by physicians thoroughly trained in these therapies.
So for example, if a receptor for GH in the brain is overly up-regulated, the receptor can shut down. A nice for instance is a peptide that is used for up regulating GH in muscles – MK0677, an oral GHRP. Well, it helps the muscles grow the more it’s used. However, once you hit a certain dose of it, it begins to oversaturate an anxiety (and fear) controlling GH receptor in the brain in a matter that shuts it down. Right. That’ss… Bad. Remember, it takes a great deal of time for this to occur, and a great deal of neglect. But it is a risk. So there are time use limits.
Also, the excessive up regulation of any beneficial peptide producing a sweet spot of returning a stressed or diseased cell to ideal physiologic homeostasis could lead to an overdrive of mitochondrial or nuclear genomic machinery, creating excessive free radicals. This could lead to shut down of portions of the electron transport chain with in the mitochondria. A lack of rest from such an overdrive from such an excess of a peptide is where problems are seen. The cell can only do so much for so long. And for every cytochrome that is shut down in the mitochondria and not producing electron transport any longer, there is less ATP made. With decreased ATP production, you have decreased the efficiency of the mitochondria. Doesn’t sound like a bad harm, but it’s also undesirable, and not what the goal was in the first place with peptide up regulation of GH – creating an ideal sweet spot of homeopathy. Overwhelming the cells of a tissue obviously lead to cell death, fibrosis, and organ dysfunction.
Really the only other downside to peptides – side effects of the metabolites of peptides – is exhaustively prevented by this growing industry because they study the potential molecules fragments of the naturally occurring peptide or synthetic peptides being administered more exhaustively than any drugs that have ever been rolled out before. But these peptides are already so small to begin with, that their even smaller degradation products, always carefully studied, are well tolerated and cleared without any side effects.
So, GH is good for our cells – it produces an anti-aging effect, it helps memory.
However, the FDA specifically forbids use of GH in adults in anti-aging except in AIDS (anti-AIDS medications like anti-retrovirals hurt the body’s GH response so these folks need exogenous GH) or human growth hormone deficiency (GHD).
So, we can make the body make more of its own GH (up-regulate) by using peptides, intermittent fasting, and exercise. This is completely allowed. And it is completely safe, because the feedback mechanisms are all kept intact (there isn’t any exogenous GH suppressing GH production).
The only real risk of up regulating the body’s own GH is over driving the cell beyond what it can physiologically do into shut down.
It’s the same old simple but valuable theme seen in so much anti-aging and regenerative medicine: find the sweet spot.
DAVID ALLINGHAM, M.D., MS