Benefits & Risks of Peptide Therapeutics for Physical & Mental Health

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.240 | where we discuss science

00:00:03.680 | and science-based tools for everyday life.

00:00:05.880 | I'm Andrew Huberman,

00:00:10.160 | and I'm a professor of neurobiology and ophthalmology

00:00:13.200 | at Stanford School of Medicine.

00:00:15.240 | Today, we are discussing peptides.

00:00:17.600 | Peptides are a topic

00:00:18.760 | that's receiving a lot of attention these days,

00:00:21.320 | in part because of the excitement

00:00:23.000 | about the so-called GLP-1 analogs or agonists.

00:00:26.440 | GLP-1 stands for glucagon-like peptides.

00:00:29.400 | These are drugs used to treat type 2 diabetes,

00:00:32.500 | as well as drugs used to treat obesity.

00:00:35.200 | Today, we are not going to discuss the GLP-1 analogs.

00:00:38.680 | However, we are going to discuss

00:00:40.480 | some of the other peptides

00:00:41.640 | that are receiving a lot of attention these days,

00:00:44.120 | including peptides for tissue healing and repair,

00:00:47.200 | as well as peptides that impact longevity and vitality.

00:00:50.600 | Now, in principle,

00:00:51.520 | any discussion about peptides could be enormously vast,

00:00:54.900 | and that's because

00:00:55.740 | there are so many different kinds of peptides.

00:00:57.760 | And by the way, I will explain what a peptide is

00:00:59.760 | in just a few moments.

00:01:01.040 | But for instance, insulin,

00:01:02.580 | which is involved in regulating our blood sugar

00:01:04.520 | or blood glucose levels, is a peptide.

00:01:06.960 | Oxytocin, which is sometimes called the love hormone,

00:01:09.520 | although I wouldn't say that's the best description

00:01:11.640 | of what oxytocin is.

00:01:13.040 | It's a neuropeptide/hormone

00:01:15.600 | that is involved in everything

00:01:16.720 | from pair bonding to socialization,

00:01:18.400 | but a bunch of other things as well.

00:01:20.280 | Those are just two examples of peptides

00:01:21.960 | that are familiar to most people, at least by name,

00:01:24.600 | and that exist within the tens of thousands,

00:01:27.320 | if not hundreds of thousands of different peptides

00:01:29.560 | that exist within our brain and body.

00:01:31.960 | Today's discussion is going to focus on peptides

00:01:34.560 | that are increasingly being used for therapeutic purposes.

00:01:38.080 | And I want to point out something very important

00:01:40.100 | about this topic area.

00:01:41.640 | First of all, it is a topic area

00:01:43.820 | for which there is a lot of confusion.

00:01:46.280 | The mere naming of the peptides is confusing.

00:01:48.400 | Oftentimes they're referred to simply by virtue

00:01:50.520 | of acronyms and numbers like BPC-157 or MK-677,

00:01:55.080 | et cetera, et cetera,

00:01:56.300 | such that if you're not really familiar with them,

00:01:58.160 | it can be a bit overwhelming and confusing.

00:02:00.600 | Today, I'm going to provide

00:02:01.680 | a very simple organizational framework

00:02:03.600 | that will allow you to understand

00:02:05.220 | what these different therapeutic peptides are,

00:02:07.840 | why certain ones may be advantageous for certain purposes,

00:02:11.640 | of course, also highlighting the potential risks

00:02:13.800 | and in some case, outright dangers,

00:02:16.040 | and I'll tell you how they each work alone

00:02:17.960 | and in combination toward achieving specific physical

00:02:21.440 | and in some cases, even mental health goals.

00:02:23.760 | I'd be remiss if I didn't say at the outset here

00:02:26.480 | that a lot of what's happening

00:02:27.900 | with applied therapeutic peptide biology

00:02:30.540 | falls into one of three categories.

00:02:32.420 | There are peptides that are being prescribed by physicians.

00:02:35.620 | So these are prescription peptides for specific purposes.

00:02:38.660 | These are FDA approved.

00:02:40.180 | There are other peptides that reside

00:02:41.820 | in kind of a gray market area.

00:02:43.960 | You can purchase them online,

00:02:45.940 | but the safety and efficacy of those peptides

00:02:49.580 | is a bit questionable, in some cases, very questionable.

00:02:52.420 | And I'll give you some filters to determine

00:02:54.320 | which category certain peptides fall into.

00:02:56.800 | And then of course, there's the black market peptides.

00:02:59.300 | It is possible to buy peptides online

00:03:02.220 | through any number of different sources.

00:03:04.060 | And of course, I do not suggest people

00:03:06.560 | purchase black market peptides.

00:03:08.140 | It's very clear that a lot of them are contaminated

00:03:10.300 | with things that both in the short term,

00:03:12.300 | but especially in the longterm can be problematic.

00:03:15.000 | So if you're interested in understanding

00:03:16.680 | or using therapeutic peptides,

00:03:18.620 | today's episode is for you.

00:03:20.320 | Before we begin, I'd like to emphasize

00:03:22.020 | that this podcast is separate

00:03:23.620 | from my teaching and research roles at Stanford.

00:03:25.900 | It is however, part of my desire and effort

00:03:28.020 | to bring zero cost to consumer information

00:03:29.900 | about science and science related tools

00:03:31.940 | to the general public.

00:03:33.400 | In keeping with that theme,

00:03:34.500 | I'd like to thank the sponsors of today's podcast.

00:03:37.420 | Our first sponsor is Martina.

00:03:39.260 | Martina makes loose leaf and ready to drink yerba mate.

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00:05:04.120 | by giving you real-time feedback on your diet

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00:05:08.380 | Now, blood glucose, sometimes referred to as blood sugar,

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00:05:17.120 | One of the best ways to maintain focus and energy

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00:06:19.160 | Now, if there's one thing I've consistently emphasized

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00:06:25.960 | And of course, I'm always telling people

00:06:27.480 | that they should get sunlight in their eyes

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00:07:44.060 | So what is a peptide?

00:07:45.240 | A peptide is a small protein

00:07:47.220 | that's made up of little chains of amino acids.

00:07:50.280 | Now, the moment people hear protein,

00:07:51.880 | they usually think proteins that you eat,

00:07:54.080 | or perhaps they think about four calories per gram

00:07:56.960 | of protein and that sort of thing.

00:07:58.640 | Keep in mind that we have lots of different kinds

00:08:00.500 | of proteins within our body

00:08:02.140 | that have nothing to do with the proteins that we eat.

00:08:04.120 | Now, it is true that many of the amino acids

00:08:06.240 | that comprise peptides,

00:08:08.240 | as well as other proteins in the body,

00:08:09.800 | come from the foods that we eat,

00:08:11.740 | because the amino acids, again,

00:08:13.000 | are the building blocks of peptides and other proteins.

00:08:16.500 | The basic way that we define a peptide

00:08:19.480 | is that it tends to be a small protein,

00:08:21.960 | meaning chains of anywhere from two to 50 amino acids.

00:08:25.900 | That's really the strict definition of a peptide.

00:08:28.280 | However, oftentimes, peptides that are a little bit bigger,

00:08:31.560 | so maybe 75 or 100 amino acids in length,

00:08:35.320 | will also be considered a peptide.

00:08:37.480 | Now, if you start combining different peptides together,

00:08:40.040 | you get what's called polypeptides,

00:08:41.680 | and many of the proteins in the body are polypeptides.

00:08:44.400 | So just to get a mental image of what a peptide is,

00:08:46.720 | a peptide basically looks like beads on a string

00:08:50.520 | where there are two to 100 beads,

00:08:53.320 | and each of those beads represents a different amino acid,

00:08:56.400 | and the arrangement of each amino acid

00:08:58.520 | relative to one another,

00:08:59.880 | that is, their order along that string,

00:09:01.880 | determines what the peptide is and what the peptide does.

00:09:05.360 | The other thing that's important to understand

00:09:06.760 | about peptides is that some peptides are hormones,

00:09:09.680 | other peptides are merely called peptides, proteins,

00:09:12.880 | others are neuromodulators,

00:09:15.240 | meaning they adjust the activity of neurons,

00:09:17.280 | and some peptides multitask and do many things.

00:09:20.160 | In fact, I think it's fair to say that most peptides

00:09:22.880 | have what are called pleiotropic effects,

00:09:25.220 | meaning they affect many different aspects of cells.

00:09:28.600 | And this is very important to understand

00:09:30.540 | because unlike a lot of our discussion on this podcast

00:09:33.500 | about dopamine or about specific hormones

00:09:35.800 | like testosterone or estrogen,

00:09:38.200 | when we talk about peptides, especially therapeutic peptides,

00:09:41.680 | oftentimes we're talking about a single peptide

00:09:44.280 | that does a bunch of different things

00:09:45.960 | depending on the cell type, the time of day or night

00:09:48.900 | that that peptide is present,

00:09:50.560 | and even the different so-called downstream effects

00:09:53.320 | of the peptide.

00:09:54.200 | What do I mean by downstream effects?

00:09:55.820 | Well, when a peptide binds to a receptor on a cell surface,

00:10:00.400 | okay, and you can just think of that process

00:10:02.060 | as a little parking spot on the surface of a cell

00:10:04.640 | and the peptide, if it's available,

00:10:06.400 | will bind to that receptor and then set in motion

00:10:09.400 | a kind of bucket brigade,

00:10:11.060 | a sort of conveyor belt of cellular processes.

00:10:14.080 | For instance, activating one pathway for cellular growth

00:10:17.160 | and another pathway for cell migration,

00:10:20.240 | for the cell to actually move,

00:10:21.600 | and maybe another pathway to talk to another cell

00:10:24.360 | to stimulate, say, the growth of blood vessels.

00:10:26.360 | In other words, lots of different or pleiotropic effects.

00:10:29.660 | This is important because when we're talking

00:10:31.520 | about peptide therapeutics, rarely, if ever,

00:10:34.240 | are we talking about a very targeted

00:10:36.360 | and very specific effect of these peptides.

00:10:38.760 | And this is important both in terms of thinking

00:10:41.000 | about what effects you're going to get

00:10:43.280 | of taking a given peptide if you decide to do that,

00:10:45.800 | as well as potential side effects,

00:10:47.560 | as well as things like how to adjust dosage

00:10:50.200 | and how long to take a peptide,

00:10:51.660 | whether or not to cycle the peptide, et cetera.

00:10:54.020 | So I just gave you a very simple description

00:10:55.700 | of what a peptide is and the fact that they have pleiotropic,

00:10:58.420 | meaning many different effects both within cells

00:11:00.720 | and across different cell types,

00:11:02.400 | and of course, across different organ systems.

00:11:05.220 | So rarely, if ever, will you hear

00:11:07.520 | that a peptide does one thing.

00:11:08.960 | Most often, a peptide does anywhere from four

00:11:11.600 | to maybe even 1,000 different things.

00:11:13.760 | And again, we can go back to our basic examples of peptides

00:11:16.960 | like insulin, like oxytocin, and say, for instance,

00:11:20.880 | oxytocin, it's known to be involved

00:11:22.600 | in milk letdown during lactation.

00:11:25.740 | It's also known to be involved in pair bonding

00:11:28.180 | in both males and females,

00:11:29.640 | as well as pair bonding between parent and child,

00:11:32.440 | maybe even parent and pet.

00:11:34.220 | So the point is that

00:11:35.060 | if you want a specific biological effect,

00:11:37.020 | maybe you want to repair a given injury,

00:11:39.000 | or you'd like to get more growth hormone in order,

00:11:42.040 | I don't know, to get leaner

00:11:43.440 | or to recover from exercise more quickly

00:11:45.540 | or to feel more vitality.

00:11:47.360 | Yes, there are peptides that can impact those pathways,

00:11:50.040 | but always, always, always, if you take peptides,

00:11:52.640 | especially therapeutic peptides designed to promote activity

00:11:56.560 | within a given pathway for a specific purpose,

00:11:59.080 | you are going to activate other pathways as well.

00:12:01.600 | There's simply no way to remove the pleiotropic feature

00:12:04.600 | of peptide therapeutics.

00:12:06.140 | Nowadays, there's a lot of interest

00:12:07.840 | and indeed growing interest in peptide therapeutics.

00:12:11.000 | And there are really three different paths

00:12:12.280 | by which people obtain these peptides.

00:12:14.600 | The first is by prescription

00:12:16.000 | from a board-certified medical doctor.

00:12:18.140 | So some peptides have been approved for one use,

00:12:20.920 | but they can be prescribed also for off-label use.

00:12:23.560 | And here we're talking about FDA-approved,

00:12:26.560 | clinically-tested peptides.

00:12:29.000 | But in many cases, they've been clinically tested

00:12:30.800 | for one particular area of medicine.

00:12:33.080 | So for instance, the peptide sermorelin,

00:12:35.420 | which promotes the release of growth hormone,

00:12:37.180 | has been FDA-approved for the treatment of short stature,

00:12:40.580 | but it is often now prescribed for other things as well,

00:12:44.460 | where a physician and their patient agree

00:12:46.440 | that augmenting the growth hormone pathway would be useful.

00:12:49.640 | Now, regardless of the specific use in mind,

00:12:51.440 | it's absolutely clear that the safest and best situation,

00:12:55.200 | if one is going to use therapeutic peptides,

00:12:57.960 | is to use prescription therapeutic peptides,

00:13:01.360 | where the prescription comes

00:13:02.440 | from a board-certified physician.

00:13:03.820 | And the reason for that is several fold.

00:13:05.320 | First of all,

00:13:06.160 | sometimes these peptides come from pharma companies,

00:13:08.680 | other times they are made by a compounding pharmacy,

00:13:11.240 | but in both situations,

00:13:13.360 | they are cleaned of what's called lipopolysaccharide, or LPS.

00:13:18.040 | LPS is something that can accumulate

00:13:19.640 | in the manufacturing process of some of these peptides,

00:13:22.280 | and it's something that you really want to remove

00:13:24.360 | from the peptide before you ingest it or inject it.

00:13:26.880 | Most peptides are injected,

00:13:28.180 | either subcutaneously or into the muscle,

00:13:29.960 | although some can be taken orally or even a topical cream.

00:13:32.720 | We'll talk a little bit about different modes of delivery

00:13:35.280 | a little bit later.

00:13:36.680 | In any case, getting the LPS out

00:13:39.840 | and making sure that the peptide is pure is very important.

00:13:43.280 | The reason is that LPS causes an immune response.

00:13:46.120 | And while a tiny amount of LPS

00:13:48.680 | might not cause a massive immune response,

00:13:50.980 | the accumulation of many, many LPS exposures

00:13:53.880 | can start to become problematic.

00:13:55.560 | And the other sources of peptides,

00:13:57.060 | which are gray market and black market,

00:13:59.120 | oftentimes do contain the same peptide

00:14:02.440 | that one would get from a prescription

00:14:05.320 | from a board-certified physician,

00:14:07.000 | but very often they haven't cleaned out

00:14:09.600 | the lipopolysaccharide, they haven't removed the LPS,

00:14:12.480 | and that can start to create problems over time.

00:14:14.460 | And of course, in the case of black market sources,

00:14:18.000 | especially, oftentimes the peptides are not

00:14:20.720 | what they claim to be on the label

00:14:22.760 | or from a particular source.

00:14:23.920 | So that's especially problematic.

00:14:25.960 | So I want to be very clear about my stance on this.

00:14:28.420 | If you are going to explore peptide therapeutics,

00:14:31.200 | I highly, highly recommend, indeed, I implore you

00:14:34.560 | to do so with a board-certified physician

00:14:37.660 | and to acquire peptides through a reliable source

00:14:40.680 | where the LPS has been removed,

00:14:42.560 | which typically means from a pharma company

00:14:46.240 | or from a compounding pharmacy.

00:14:48.400 | Okay, so let's talk about specific peptides

00:14:51.240 | for specific purposes.

00:14:52.800 | Today, we're going to cover four general areas

00:14:55.280 | in which peptide therapeutics can be useful.

00:14:57.780 | The first is for rejuvenation and repair

00:15:00.520 | of basically any tissue, but in particular,

00:15:03.440 | muscle and connective tissue, so sports-type injuries,

00:15:06.960 | but also things like gut.

00:15:08.720 | So for people that suffer from IBS, irritable bowel syndrome,

00:15:12.200 | or from colitis, or from other gut issues,

00:15:15.540 | there is a potential use for therapeutic peptides.

00:15:18.120 | Then we're going to discuss therapeutic peptides

00:15:20.360 | for metabolism and growth of, frankly, all tissues.

00:15:23.800 | As soon as people hear metabolism and growth,

00:15:25.700 | generally, people think of fat loss and muscle growth,

00:15:28.500 | and indeed, those fall under this category,

00:15:30.240 | but there are a bunch of other tissues

00:15:31.760 | for which you may want to improve metabolism

00:15:34.320 | and perhaps growth as well, so we'll get into that.

00:15:36.940 | Then we'll discuss therapeutic peptides

00:15:38.880 | specifically for longevity, both staving off tumor growth,

00:15:42.380 | as well as potentially,

00:15:43.640 | and I want to highlight potentially, increasing lifespan,

00:15:46.880 | although this is a very experimental area at present.

00:15:49.640 | And then we'll talk about therapeutic peptides

00:15:51.880 | for increasing vitality,

00:15:53.400 | both mood and libido in both men and women.

00:15:56.320 | Okay, so let's discuss peptides

00:15:57.820 | for rejuvenation and repair of tissues.

00:16:00.520 | Now, it's pretty common to injure a given tissue,

00:16:04.180 | you know, to strain a tendon, or tear a ligament,

00:16:08.460 | or break a bone, or I don't know,

00:16:10.480 | any number of different things.

00:16:11.720 | This is just kind of part of life.

00:16:13.440 | If you play sports or if you exercise frequently,

00:16:16.520 | sooner or later, people tend to get injured.

00:16:19.040 | And when one does, there's, you know,

00:16:21.200 | a lot of different things one can do.

00:16:22.820 | There's a lot of debate nowadays

00:16:24.840 | about whether or not you should emphasize cold

00:16:26.800 | or whether or not you should emphasize heat.

00:16:28.140 | There seems to be a growing movement

00:16:29.400 | towards emphasizing the use of heat

00:16:31.200 | to increase blood flow to a given tissue

00:16:32.920 | as opposed to cold.

00:16:34.420 | We've covered some of this on other podcasts.

00:16:36.080 | We'll cover it more on future podcasts.

00:16:38.260 | But, you know, if you happen to injure yourself,

00:16:40.880 | typically what your physician will say is rest,

00:16:44.480 | maybe do some physical therapy.

00:16:46.120 | And indeed, those are excellent things to do.

00:16:48.440 | But one, of course, would ask,

00:16:50.520 | is there anything I can take

00:16:51.760 | in order to accelerate the healing of a given injury?

00:16:55.680 | And for that purpose, a lot of people over the years

00:16:58.200 | have explored the use of different peptides,

00:17:00.600 | in particular, one that exists within the body naturally

00:17:04.000 | and that is involved in wound healing and repair.

00:17:06.960 | And that peptide is BPC,

00:17:09.200 | which stands for Body Protection Compound 157.

00:17:12.920 | BPC 157 is a synthetic peptide.

00:17:16.000 | It's manufactured in a laboratory

00:17:18.520 | to resemble a peptide that exists naturally within our gut.

00:17:22.820 | Now, why would we have a naturally occurring peptide,

00:17:25.080 | a protein within our gut

00:17:26.520 | that's involved in wound healing and repair?

00:17:29.160 | Now, the answer to this isn't entirely clear.

00:17:31.280 | And as I always say,

00:17:32.140 | anytime you want to answer a question

00:17:34.080 | about kind of why something evolved to be a particular way,

00:17:37.200 | you have to remember that neither I nor anyone else

00:17:39.300 | was involved in the design phase.

00:17:40.820 | It just is what it is.

00:17:41.960 | So we have to be careful about making up just so stories

00:17:44.440 | about why something is doing what it's doing

00:17:47.080 | or how it got there.

00:17:48.520 | So why would there be a peptide within the gut

00:17:50.380 | that's involved in tissue healing and repair?

00:17:53.200 | Well, in order to understand that,

00:17:54.640 | it's important to understand that the lining of your gut

00:17:58.080 | all along its length

00:17:59.680 | involves a bunch of different layers of cells

00:18:01.700 | that turn over at a pretty frequent rate.

00:18:04.040 | So unlike your brain cells,

00:18:05.720 | that for instance, after about age 25,

00:18:07.840 | you're not adding or deleting many brain cells,

00:18:10.520 | at least provided there's no injury

00:18:12.240 | or nerve degenerative disease,

00:18:14.060 | you're not removing a lot of those brain cells,

00:18:16.000 | but you're also not adding many brain cells.

00:18:17.760 | There are a few areas of the brain,

00:18:19.080 | like the olfactory bulb and the dentate gyrus

00:18:21.080 | or the hippocampus where there is some turnover.

00:18:22.760 | But for the most part,

00:18:23.600 | the neurons you have at about age 25

00:18:25.460 | are the neurons that you're going to have

00:18:26.660 | for the rest of your life.

00:18:28.040 | Your gut is very different.

00:18:29.100 | Within the milieu of the gut,

00:18:30.660 | you have a lot of turnover of cells.

00:18:33.080 | And the turnover of cells in the gut is in many ways,

00:18:36.160 | the same sort of turnover process

00:18:37.960 | that's involved in wound healing and repair.

00:18:39.660 | Like if you cut your skin,

00:18:40.760 | another tissue or organ in this case,

00:18:43.280 | that involves a lot of turnover of cells,

00:18:45.500 | because as you know, if you cut your skin,

00:18:47.860 | at some point it will heal up,

00:18:50.060 | first there'll be a scab,

00:18:51.220 | then that scab will give way

00:18:53.020 | as the tissue underneath it mends.

00:18:54.500 | And that mending of the tissue

00:18:55.500 | is the addition of new skin cells

00:18:57.060 | as well as other cell types.

00:18:58.740 | So the fact that there is a peptide in our gut

00:19:01.860 | that can be involved in tissue turnover

00:19:04.860 | and tissue turnover is equivalent to tissue repair

00:19:07.300 | is not all that surprising.

00:19:09.100 | Now, it's important to understand

00:19:10.140 | that anytime we're discussing tissue rejuvenation,

00:19:12.660 | that is cellular turnover or tissue repair,

00:19:15.660 | so any kind of wound healing,

00:19:16.820 | a small wound or a big wound,

00:19:18.720 | it almost certainly is going to involve angiogenesis,

00:19:21.620 | which is the development of new vascular supply

00:19:25.060 | or blood supply.

00:19:26.500 | Now, of course, vascular supply arrives

00:19:29.240 | by capillaries, veins, and arteries.

00:19:31.920 | And typically when we're talking about angiogenesis

00:19:34.860 | in the context of tissue rejuvenation and repair,

00:19:37.200 | we're talking about the addition of new capillaries

00:19:39.420 | and or blood vessels.

00:19:40.780 | And that means the addition of new

00:19:42.540 | what are called endothelial cells,

00:19:44.420 | which are the cells that make up the walls

00:19:46.020 | of those blood vessels.

00:19:47.580 | So put simply, if you want to rejuvenate a tissue

00:19:49.940 | or you want to repair a tissue,

00:19:52.060 | you need additional blood supply.

00:19:54.180 | And one of the clear effects of BPC-157

00:19:57.300 | is to both encourage cellular turnover

00:20:00.620 | as well as cellular migration,

00:20:01.960 | so new cells and cells moving into a given area,

00:20:04.820 | as well as new blood supply

00:20:06.980 | through the promotion of this process we call angiogenesis.

00:20:10.400 | So you can imagine, for instance,

00:20:11.500 | that maybe you injure your elbow

00:20:13.860 | and you do so in a way that impacts

00:20:15.540 | a bunch of different tissues.

00:20:16.480 | Maybe some of the nerve cells,

00:20:17.820 | the neurons there are severed, okay, or crushed.

00:20:21.460 | So that might lead to some pain there,

00:20:23.200 | but it might also lead to some inability

00:20:24.980 | to move that joint or that limb

00:20:27.320 | as well as you could previously.

00:20:28.980 | Probably also some damage or some crushing

00:20:30.860 | to some ligament tissue and some tendon tissue,

00:20:33.620 | maybe even to some musculature.

00:20:34.900 | A bunch of different tissues are impacted.

00:20:36.860 | And one of the things that BPC-157

00:20:39.180 | has been shown to do in animal studies,

00:20:41.480 | and I really want to emphasize animal studies

00:20:43.700 | because that's where the vast, vast, vast majority

00:20:46.040 | of data on BPC-157 come from.

00:20:49.120 | Well, it's been shown to increase blood flow

00:20:52.680 | to a given area by virtue of increased angiogenesis.

00:20:55.840 | So basically to promote the development

00:20:57.560 | of new blood vessels to the entire injury site.

00:21:01.520 | And the way it does that is very interesting.

00:21:03.640 | BPC-157 somehow is able to recognize injured blood vessels

00:21:08.760 | and injured capillaries,

00:21:10.060 | and then to promote the activity of a given enzyme

00:21:12.420 | called ENOS or endothelial nitric oxide synthase,

00:21:17.020 | which then causes more blood vasculature to form

00:21:20.340 | at the injury site and around the injury site.

00:21:23.440 | That in turn allows for the delivery, not just of blood,

00:21:26.180 | but for the stuff that's contained within blood,

00:21:27.880 | including growth factors that then promote

00:21:29.980 | the further rejuvenation of different cell types

00:21:32.700 | in the given area.

00:21:33.540 | So the things that could potentially lead

00:21:34.960 | to repair of muscle, repair of ligament,

00:21:36.740 | repair of tendon, et cetera.

00:21:38.380 | And then BPC-157 is known to further encourage the growth

00:21:42.260 | of capillaries and veins within the injury area.

00:21:45.240 | So it both calls in the development of new vasculature

00:21:48.300 | and it promotes the growth of that new vasculature.

00:21:50.940 | BPC-157 is also known from animal studies

00:21:53.660 | to encourage fibroblast migration and growth

00:21:56.840 | within a site of injury.

00:21:58.180 | Fibroblasts are a key cell type within an injury,

00:22:01.680 | and they provide some of the really firm, strong substrate

00:22:04.920 | for bridging injuries and that allow different things

00:22:07.580 | like tendons and ligaments to restore themselves

00:22:10.340 | from say torn or partially torn

00:22:12.540 | to a complete tendon or ligament.

00:22:14.500 | Now there's a very long and kind of interesting history

00:22:17.080 | of the use of gastric juices.

00:22:19.760 | Okay, I know the term might make a few people queasy,

00:22:22.260 | but gastric juices to promote tissue healing and repair.

00:22:25.820 | Now there's a whole history of focusing on gastric juices

00:22:29.300 | or at least the stomach environment

00:22:31.280 | for keeping given tissues alive

00:22:33.820 | so that they can be repaired later.

00:22:35.540 | I know this sounds a bit gruesome,

00:22:36.720 | but one can find in the historical medical literature

00:22:39.920 | instances of people say severing off a finger

00:22:43.580 | or even a hand or things of that sort.

00:22:47.040 | And then it being placed by a surgeon of course,

00:22:49.300 | or in some cases, these were battlefield situations

00:22:52.820 | into the gut as a way to preserve that finger or hand

00:22:57.740 | and keep it alive essentially.

00:22:59.540 | And then to graft it back on

00:23:01.020 | or to make an attempt to graft it back on

00:23:03.660 | so that the person could then use those fingers

00:23:05.740 | or that hand again.

00:23:06.860 | And while not always successful,

00:23:08.380 | it was clear or at least the idea started to form

00:23:12.180 | that tissues that were placed inside the milieu of the gut

00:23:15.620 | stood a better chance of being grafted back on.

00:23:17.820 | Now you could think of a number of different factors

00:23:19.500 | that could impact the improved grafting

00:23:21.760 | of tissues placed in the gut

00:23:23.740 | until the graft could take place.

00:23:25.580 | You know, it could be the heat of the environment.

00:23:28.180 | It could be the fact that the hand or finger

00:23:31.260 | is not exposed to things out in the world.

00:23:33.140 | So less bacteria, et cetera.

00:23:34.860 | Nonetheless, physicians were intrigued by the idea

00:23:36.820 | that maybe something within the gut itself

00:23:38.700 | and in particular within gastric juices

00:23:41.020 | were beneficial for preserving

00:23:42.540 | and maybe even rejuvenating tissues.

00:23:44.460 | And one particular peptide compound

00:23:46.220 | turned out to be BPC, body protection compound,

00:23:48.780 | which again is synthesized as BPC-157.

00:23:52.020 | So there's a real logic here.

00:23:53.700 | But what we haven't really addressed is

00:23:55.980 | if one has an injury, let's say to the hand

00:23:59.060 | or to the arm or to the leg or to the ankle

00:24:02.020 | or to the Achilles tendon,

00:24:03.600 | how is it that body protection compound

00:24:05.460 | that normally would exist within the gut

00:24:07.780 | actually access that injured tissue?

00:24:10.220 | Now, this still remains somewhat of a mystery.

00:24:12.220 | It is clear that BPC-157 can exit the gut,

00:24:15.500 | but how it gets traffic to particular sites

00:24:17.500 | within the body that are injured still isn't clear.

00:24:20.180 | That said, within the community of people

00:24:22.260 | that use BPC-157 for therapeutic reasons

00:24:25.020 | for tissue rejuvenation and repair,

00:24:27.100 | there's sort of been an ongoing debate

00:24:28.420 | as to whether or not you can take it systemically,

00:24:31.160 | that is to inject it or even take it orally,

00:24:34.100 | and that it will find the site of injury, right?

00:24:36.220 | It'll direct itself to the site of injury,

00:24:38.980 | or whether or not it's more beneficial

00:24:40.460 | to inject it directly to the site of injury.

00:24:43.020 | And here there's really no formal science.

00:24:44.940 | I want to be really clear.

00:24:46.420 | When we talk about BPC-157,

00:24:48.460 | we can look to a pretty large literature

00:24:50.620 | of peer-reviewed studies dating back to about 1993

00:24:53.780 | is when the first kind of rigorous study

00:24:55.460 | of BPC-157 really began.

00:24:58.140 | And there are a lot of studies in rats, in mice,

00:25:00.920 | in a few other species as well.

00:25:02.740 | To my knowledge, there is only one study on humans,

00:25:06.260 | and it's not a clinical trial.

00:25:07.940 | And frankly, it's not the best performed study,

00:25:11.020 | and that's putting it mildly.

00:25:12.120 | It's more kind of self-report

00:25:14.040 | of people recovering from a given injury,

00:25:16.160 | whether or not they took BPC-157 or they didn't.

00:25:18.860 | So when we talk about BPC-157,

00:25:20.740 | we're talking about a pretty unusual circumstance

00:25:23.300 | whereby many, many people are now taking it,

00:25:26.400 | very likely hundreds of thousands,

00:25:27.980 | perhaps even now into the millions.

00:25:30.060 | But we actually have essentially no human data

00:25:33.280 | as to how BPC-157 works in humans and why it does seem,

00:25:38.280 | because this seems to be the "anecdota"

00:25:41.320 | to accelerate healing of a variety of different injuries.

00:25:45.360 | Okay, so it's an unusual circumstance,

00:25:47.080 | and it's kind of an unusual thing

00:25:48.320 | for us to talk about here on the podcast.

00:25:50.520 | Yes, we've talked about supplements,

00:25:51.820 | and yes, we've talked about different hormone therapies,

00:25:53.760 | and yes, we've talked about any number of different things,

00:25:55.940 | but it's pretty unusual to have so much animal literature.

00:25:59.360 | I even would go so far as to say quality studies

00:26:02.440 | of BPC-157 and its effects in animal models,

00:26:06.120 | such as rats and mice,

00:26:07.440 | and such a dearth of formal rigorous exploration

00:26:10.080 | of BPC-157 in humans.

00:26:11.620 | And at the same time, a, gosh, let's just call it what it is,

00:26:15.480 | a really rich set of "anecdota,"

00:26:18.380 | meaning that many, many people,

00:26:19.960 | perhaps even most people who take BPC-157,

00:26:23.280 | and by the way, the typical route of taking BPC-157

00:26:25.880 | is either to inject it subcutaneously or into the muscle,

00:26:29.660 | and to do that, regardless of where the injury is,

00:26:32.200 | they'll do that in one particular site,

00:26:33.680 | so subcutaneously, just a few inches off the belly button,

00:26:36.920 | or into the shoulder or something of that sort,

00:26:40.440 | if they're doing it intramuscularly,

00:26:42.080 | or in some cases, people will direct it

00:26:43.760 | to the site of injury by injecting more local,

00:26:46.520 | like if you have an elbow injury,

00:26:47.560 | they'll put it into the muscle right above the elbow

00:26:49.000 | or subcutaneously right above the elbow.

00:26:51.020 | And we're now in a situation where we don't know

00:26:53.340 | if we're dealing with pure placebo effect

00:26:55.240 | or we are dealing with real effects,

00:26:57.760 | and so because of the lack of the human clinical studies,

00:26:59.980 | we don't know whether or not we're dealing

00:27:01.240 | with a situation of robust placebo effects.

00:27:04.480 | I did an episode all about placebo effects,

00:27:06.160 | and placebo effects are and can be oh so real.

00:27:09.080 | They really can really trick you into thinking

00:27:12.380 | that a given compound is doing something

00:27:14.040 | when in fact it's not doing anything different

00:27:15.920 | than would an injection of saline, of salt water,

00:27:18.840 | but in this case, there's just such an overwhelming amount

00:27:22.740 | of what I call "anecdota,"

00:27:25.080 | and there are so many people using BPC-157 now

00:27:27.940 | and are interested in starting to use BPC-157

00:27:31.120 | that I'd be remiss if I didn't discuss it

00:27:32.640 | despite this gap in the human clinical literature.

00:27:35.560 | So what do we know from the anecdota?

00:27:37.640 | The anecdota seem to indicate that the mode of delivery,

00:27:40.200 | that is whether or not systemic or local,

00:27:41.840 | doesn't seem to matter that much,

00:27:43.840 | although some people, for whatever reason,

00:27:45.920 | will purport that local injections serve recovery

00:27:49.840 | of the tissue more readily than systemic injections.

00:27:53.420 | Now, there are a couple things to understand

00:27:54.600 | about BPC-157 besides the fact that in animal studies,

00:27:57.720 | it's been shown to increase fibroblast migration

00:28:00.640 | to a site of injury as well as endothelial cell

00:28:03.200 | and vascular growth to a site of injury.

00:28:05.360 | And the first thing is that injury seems to be important.

00:28:08.480 | There does seem to be something that the injury signals

00:28:12.000 | to BPC-157 to create new vasculature

00:28:15.680 | and fibroblast growth there at the site of injury.

00:28:18.540 | There's no evidence from these animal studies,

00:28:20.540 | at least to my knowledge,

00:28:21.880 | that BPC-157 systemically increases vascular growth,

00:28:25.760 | although one could imagine that it might, right?

00:28:28.560 | And for that reason,

00:28:29.720 | I'll talk about some cautionary notes about BPC-157

00:28:32.480 | as it relates to tumor growth and cancers and diseases,

00:28:35.680 | in particular of the eye,

00:28:37.000 | that involve overgrowth of vasculature.

00:28:39.480 | But before I do that,

00:28:40.320 | I want to talk a little bit about the safety of BPC-157.

00:28:43.520 | One of the reasons why it's being used so extensively

00:28:46.520 | is that it does seem to have very high safety profiles,

00:28:49.320 | at least with respect to the lethal dosing, right?

00:28:52.320 | In order to find out the lethal dose of something,

00:28:54.760 | as you can imagine,

00:28:55.840 | unfortunately, the way these studies are done

00:28:57.360 | is they give animals more and more,

00:28:59.240 | that is higher and higher doses of a given compound,

00:29:01.320 | find out at what point about 50% of the population

00:29:05.200 | of those animals starts to die,

00:29:06.360 | and then that's the so-called LD50,

00:29:08.120 | or at least that's one crude way of describing it.

00:29:10.720 | The LD50 of BPC-157 is incredibly high, okay?

00:29:17.080 | It is as high as two grams, okay?

00:29:19.740 | Two grams, 2,000 milligrams, that is,

00:29:21.960 | per kilogram of body weight.

00:29:23.600 | Now, that does not mean, please hear me on this,

00:29:26.480 | that does not mean that anyone should be taking

00:29:28.920 | high dosages of BPC-157.

00:29:30.840 | The typical therapeutic doses that are prescribed

00:29:34.240 | are anywhere from 300 to 500 micrograms subcutaneously,

00:29:38.820 | maybe two or three times per week.

00:29:41.100 | And that is typically done for a course of about eight weeks

00:29:45.160 | and then people typically cycle off

00:29:46.880 | for anywhere from eight to 10 weeks.

00:29:48.880 | Now, when I say typically, I mean typically,

00:29:51.400 | because there are individuals

00:29:52.440 | that take BPC-157 consistently.

00:29:54.700 | They just take it every day

00:29:55.840 | and they'll just take it indefinitely without any breaks.

00:29:58.400 | I think that is a bad idea.

00:30:00.920 | And I want to also state that I am not suggesting anyone

00:30:03.840 | run out and take BPC-157.

00:30:05.880 | Today's episode is really about giving you information

00:30:08.320 | so that you can make the determination

00:30:09.720 | whether or not you even want to take BPC-157

00:30:12.240 | or another peptide.

00:30:14.080 | And of course, to really seriously consider

00:30:16.080 | the sourcing issue that we talked about earlier.

00:30:18.700 | Now, what would be a reason to avoid taking BPC-157?

00:30:22.160 | Well, the first relates to something

00:30:24.040 | that many people take BPC-157 for

00:30:26.720 | because they believe it's good for them.

00:30:27.960 | And in some cases, potentially could be,

00:30:29.720 | which is that in addition to increasing fibroblast migration

00:30:33.200 | and angiogenesis, blood vessel development

00:30:35.720 | within a site of injury,

00:30:37.600 | BPC-157 is known to have a small,

00:30:40.420 | but nonetheless meaningful impact

00:30:42.280 | on upregulating growth hormone receptors.

00:30:45.340 | Now, this can be a good thing

00:30:46.760 | if you're trying to upregulate growth hormone receptors

00:30:49.000 | at a given injury site so that growth hormone,

00:30:51.840 | which comes from the pituitary,

00:30:53.280 | and then we'll talk a bit about more later,

00:30:55.200 | then can have a heightened level of action at that tissue

00:30:58.200 | and growth hormone is involved in tissue turnover and repair.

00:31:02.160 | This is evident from childhood

00:31:03.680 | where kids heal from wounds much faster

00:31:05.960 | than adults heal from wounds.

00:31:07.840 | There's other reasons why kids heal from wounds

00:31:10.480 | more quickly than adults that relate to things

00:31:12.320 | like stuff for secreted from the thymus, et cetera.

00:31:14.620 | We'll talk about that as well.

00:31:15.980 | But this idea of increasing growth hormone receptors

00:31:18.720 | at the site of injury or around the site of injury

00:31:21.140 | by injecting BPC-157 locally to the injury

00:31:23.920 | or even taking it systemically

00:31:25.320 | is one thing that many people think of as advantageous

00:31:28.280 | and that's why they want to take BPC-157.

00:31:30.920 | However, for some people,

00:31:32.080 | perhaps people who have a tumor in a given area,

00:31:35.400 | an increase in growth hormone receptors

00:31:36.960 | in and around the tumor

00:31:38.160 | could potentially increase the growth of the tumor.

00:31:40.440 | And that's one of the major issues with BPC-157

00:31:43.200 | that's not often discussed,

00:31:44.600 | which is that if you have a tumor

00:31:46.920 | and tumors thrive on increased blood flow

00:31:49.320 | because they like to consume growth factors

00:31:51.580 | and increased blood flow means increased growth factors

00:31:53.960 | and other things that can not just sustain,

00:31:56.580 | but actually grow the tumor.

00:31:58.060 | Well, then by taking BPC-157,

00:31:59.920 | you may be either maintaining

00:32:01.740 | or accelerating the growth of a tumor

00:32:03.460 | that would otherwise be removed or stay small.

00:32:06.740 | In other words, BPC-157 is a potential tumor growth risk.

00:32:11.000 | So if you have knowledge of a given cancer

00:32:13.600 | or you're concerned about tumors at all,

00:32:15.960 | I would encourage you to be very cautious

00:32:17.600 | about the use of BPC-157.

00:32:19.560 | In fact, one way that BPC-157

00:32:21.960 | creates this increase in angiogenesis,

00:32:24.160 | this increase in vasculature

00:32:26.080 | is through upregulation of something called VEGF,

00:32:28.440 | V-E-G-F, which is vascular endothelial growth factor.

00:32:32.680 | Now, there is a common treatment for cancers,

00:32:36.400 | which is Avastin.

00:32:37.760 | Avastin is a VEGF inhibitor.

00:32:40.280 | It's a drug that's designed to fight tumors,

00:32:42.680 | to reduce tumor size,

00:32:44.240 | and does so by inhibiting VEGF.

00:32:47.520 | Whereas BPC-157 is doing the exact opposite.

00:32:50.400 | It is increasing levels of VEGF to increase angiogenesis.

00:32:53.780 | So by logical extension,

00:32:54.960 | if you're concerned about tumors or cancer of any kind,

00:32:57.640 | BPC-157 is probably not something that you want to explore.

00:33:01.240 | So if BPC-157 carries these risks,

00:33:03.460 | why are so many people interested in taking it

00:33:05.860 | or taking it?

00:33:07.200 | I think in large part,

00:33:08.080 | that's due to the fact that the anecdote about BPC-157

00:33:11.880 | is just so strong.

00:33:13.640 | People report all sorts of things,

00:33:15.400 | like they recovered from their shoulder injury much faster.

00:33:18.280 | There are these kind of outrageous claims

00:33:19.720 | about people recovering from complete tissue transections.

00:33:22.880 | And indeed there, the animal data are pretty impressive.

00:33:25.640 | I went into the data

00:33:26.480 | that looked at sciatic nerve regrowth after injury,

00:33:29.560 | Achilles tendon regrowth after injury.

00:33:31.960 | And some of these studies in rats

00:33:33.320 | involved a complete transection,

00:33:35.000 | not just a partial tear,

00:33:36.540 | but a complete cut of a given ligament or tendon

00:33:39.860 | or nerve pathway.

00:33:40.780 | And indeed the data are pretty impressive

00:33:42.980 | that when BPC-157 is applied systemically, right?

00:33:46.460 | So given, you know, at the level of the gut,

00:33:48.340 | somehow it's able to travel to the site of injury,

00:33:51.180 | recognize that something needs to be done there

00:33:53.340 | in particular angiogenesis and fibroblast infiltration.

00:33:56.460 | And it does seem that on average

00:33:59.100 | that these tissues repair faster

00:34:02.140 | than they do if BPC-157 is not provided.

00:34:04.940 | But again, the tumor concerns and the lack of human data

00:34:08.000 | are a real concern that everyone should be made aware of.

00:34:10.460 | I do not think that BPC-157

00:34:12.700 | is not without its quote unquote side effects.

00:34:15.340 | I do think that we are now in a state

00:34:17.500 | of widespread experimental use of BPC-157,

00:34:20.800 | even though it can be obtained clean without LPS

00:34:23.580 | from compounding pharmacies and by prescription.

00:34:25.880 | There are a lot of people taking BPC-157.

00:34:28.240 | And I just want to return to the point I made earlier,

00:34:30.700 | which is that, you know,

00:34:32.020 | BPC-157 is typically taken in these dosages

00:34:34.660 | of about 300 to 500 micrograms, you know,

00:34:37.020 | two to three times per week, maybe even five days per week.

00:34:40.220 | If you're going to go down this path of taking BPC-157,

00:34:43.580 | I would encourage you to take the minimal effective dose,

00:34:46.740 | to not just simply do it every day,

00:34:48.060 | and certainly to not do it continuously.

00:34:50.660 | And of course, to monitor your other health metrics

00:34:53.300 | for anything that could potentially resemble cancer

00:34:55.600 | or tumor growth.

00:34:56.460 | Because obviously stimulating angiogenesis for wound repair

00:34:59.860 | sounds like a great thing,

00:35:00.900 | recovering and being able to do your workouts

00:35:03.520 | or play your sport or move about more comfortably,

00:35:06.220 | of course, a wonderfully attractive thing to do.

00:35:08.700 | Isn't that what we all want?

00:35:09.940 | But obviously not with the trade-off of growing a tumor

00:35:12.960 | or developing a cancer or accelerating a cancer.

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00:36:43.120 | Okay, so we're still talking about peptides

00:36:45.160 | for tissue rejuvenation and repair.

00:36:47.040 | And we spent quite a bit of time on BPC-157

00:36:49.560 | because that's one getting a lot of attention nowadays.

00:36:52.120 | There's another one that's getting increasing attention

00:36:54.560 | that's worth mentioning, which is thymosin beta-4

00:36:58.080 | and a related peptide, which is TB-500,

00:37:01.060 | which is basically a truncated or a shortened version

00:37:04.060 | of the thymosin beta-4 peptide.

00:37:06.020 | Remember the peptide are these strings of amino acids

00:37:08.160 | like beads on a string.

00:37:09.520 | And thymosin beta-4 is something

00:37:11.560 | that the body produces naturally

00:37:13.100 | from this thing called the thymus,

00:37:15.500 | which is present in children

00:37:17.160 | and then disappears as we get older.

00:37:19.560 | And it's well-known, again, this is correlative,

00:37:21.500 | but it's well-known that children recover more quickly

00:37:25.800 | from injuries and indeed the degree of tissue regrowth

00:37:28.520 | and the repair of wounds with minimal scarring

00:37:31.000 | is so much greater in young children

00:37:33.160 | and in children than it is in adults.

00:37:35.600 | And this is what gave rise to the idea

00:37:37.160 | that perhaps some of the peptides

00:37:38.660 | that are secreted from the thymus,

00:37:40.240 | such as thymosin beta-4,

00:37:41.960 | could be involved in tissue rejuvenation and repair.

00:37:46.120 | And that's what led to the laboratory synthesis

00:37:48.480 | of thymosin beta-4, the full-length peptide

00:37:50.760 | made in a lab, not by the thymus,

00:37:52.640 | and then adults take it, okay?

00:37:54.920 | Or TB500, which is this truncated,

00:37:57.360 | slightly shortened version of thymosin beta-4,

00:37:59.320 | which acts similarly to thymosin beta-4,

00:38:02.040 | but has a kind of different mode of action,

00:38:03.600 | lasts a little bit longer, et cetera.

00:38:05.700 | Now, again, we're in a situation

00:38:06.960 | where there are vast amounts of animal data,

00:38:09.460 | studies on mice or rats typically,

00:38:12.020 | that show that thymosin beta-4

00:38:13.700 | can increase the rate and/or thoroughness

00:38:16.480 | of wound healing and repair.

00:38:18.520 | But again, there are more and more people

00:38:19.900 | now taking thymosin beta-4

00:38:21.900 | for the purposes of tissue rejuvenation and repair

00:38:24.640 | and report positive effects.

00:38:26.040 | Now, when we say positive effects,

00:38:27.280 | we have to stand back and say,

00:38:28.520 | well, what's the control experiment?

00:38:31.560 | How would they know how quickly they would heal

00:38:33.360 | without the thymosin beta-4?

00:38:35.000 | And there's simply no way to address that question.

00:38:37.280 | My whole purpose in doing this episode

00:38:39.040 | is to highlight how these different molecules

00:38:41.860 | ought to work, how they've been shown

00:38:43.400 | to work in animal models,

00:38:44.600 | and therefore how they might be working in humans.

00:38:47.040 | But again, in the absence of clinical trials,

00:38:49.440 | we still don't know if and how they are working in humans.

00:38:52.920 | Nonetheless, a lot of people are now starting to take,

00:38:55.260 | especially TB-500.

00:38:56.600 | It's often taken in combination with BPC-157.

00:38:59.600 | And at the level of mechanism,

00:39:01.080 | the difference between BPC-157 and thymosin beta-4

00:39:04.400 | is that thymosin beta-4 really promotes the growth

00:39:08.280 | and infiltration of all sorts of different cell types

00:39:10.760 | associated with tissue rejuvenation

00:39:12.880 | and especially wound healing and repair.

00:39:14.720 | It's been shown to promote stem cell proliferation.

00:39:17.640 | It's been shown to increase the growth

00:39:20.400 | of the so-called extracellular matrix,

00:39:22.080 | the stuff around the cells

00:39:23.200 | that keeps the area around the cells kind of rigid

00:39:25.520 | so that the tissue or the organ has more stability, right?

00:39:29.280 | You can't just have a bunch of cells

00:39:30.440 | with a bunch of empty space around them

00:39:32.520 | where they can move about.

00:39:33.540 | You want to have some rigidity to the whole thing.

00:39:35.820 | So the idea is that thymosin beta-4

00:39:37.640 | is promoting the aggregation of a bunch of things

00:39:39.920 | associated with tissue healing.

00:39:42.080 | I've noticed out there that a lot of people

00:39:43.440 | talk about TB-500, that is thymosin beta-4,

00:39:46.480 | in the context of being growth-promoting.

00:39:48.680 | As far as I know, it isn't growth-promoting.

00:39:50.600 | It doesn't impact the growth hormone pathway

00:39:52.520 | or other pathways associated with tissue growth.

00:39:54.580 | Rather, it's involved in tissue repair.

00:39:56.900 | So what I just discussed are the two major players

00:39:58.800 | or the two most often used peptides nowadays

00:40:02.020 | for tissue rejuvenation and repair.

00:40:03.960 | We've got BPC-157, which you can just basically

00:40:06.680 | frame up in your mind as promoting angiogenesis

00:40:08.800 | and wound repair through a variety of mechanisms,

00:40:10.980 | but mainly the addition of new vasculature to the wound site.

00:40:14.200 | And then we've got thymosin beta-4,

00:40:16.000 | which is sometimes referred to as TB-500,

00:40:18.560 | which is just a shorter synthesized version

00:40:20.920 | of thymosin beta-4, which is a molecule

00:40:23.240 | known to come from the thymosin children.

00:40:25.880 | Whether or not it's solely responsible,

00:40:27.600 | I doubt it's solely responsible, in fact,

00:40:29.760 | for the better tissue healing and repair

00:40:32.200 | seen in children as opposed to adults, we don't know.

00:40:35.340 | And yet it does seem, at least anecdotally,

00:40:38.080 | that people are taking TB-500, again,

00:40:40.520 | either alone or in combination with BPC-157,

00:40:43.240 | and at least to their mind, are reporting more thorough

00:40:46.400 | or more rapid tissue rejuvenation and repair.

00:40:49.360 | So the next category of peptide effects

00:40:51.260 | that I'd like to talk about are the effects

00:40:53.440 | of certain peptides on metabolism and growth.

00:40:56.160 | And any discussion about metabolism and growth,

00:40:58.740 | by definition, has to include a discussion

00:41:00.740 | about growth hormones.

00:41:01.760 | So basically where we're headed is a discussion

00:41:03.940 | about peptides that can increase amounts of growth hormone

00:41:07.120 | that are released in our brain and body

00:41:09.160 | to have specific effects,

00:41:10.600 | in particular, increases in metabolism

00:41:13.160 | and increases in either muscle growth,

00:41:15.400 | and in some cases, repair of tissues as well,

00:41:17.600 | although mainly muscle growth and fat loss.

00:41:20.940 | For those of you that aren't familiar with growth hormone,

00:41:22.780 | growth hormone is a hormone that we naturally make.

00:41:25.160 | It's secreted from a gland called the pituitary gland.

00:41:27.720 | The pituitary sits near the roof of the mouth,

00:41:30.400 | and it extends out of the stalk of the brain

00:41:33.760 | such that it can release hormones

00:41:35.080 | into the general bloodstream.

00:41:36.960 | The pituitary is connected to the brain, however,

00:41:40.000 | so it can get input from a brain area

00:41:41.780 | called the hypothalamus, and within the hypothalamus,

00:41:44.160 | there are neurons that can send signals to the pituitary,

00:41:47.040 | telling it to either release growth hormone

00:41:49.120 | or to suppress the release of growth hormone.

00:41:51.620 | Now, early in life, when we are infants, children,

00:41:54.200 | teenagers, and so on, we secrete tons of growth hormone,

00:41:57.920 | in particular, during the early hours of sleep each night.

00:42:01.460 | We also secrete growth hormone a little bit

00:42:03.120 | throughout the day, but it's really in sleep

00:42:05.160 | in which we have the greatest degree

00:42:06.660 | of growth hormone release.

00:42:07.840 | This is one reason why babies and kids and teenagers

00:42:10.320 | sleep so much is there's a lot of growth hormone release,

00:42:13.560 | and we tend to grow, that is the tissues and limbs

00:42:16.320 | of our body tend to grow during sleep.

00:42:19.160 | Now, it's been well-documented that after about age 30,

00:42:23.080 | which is typically when people experience

00:42:25.120 | their full stature, their full height,

00:42:26.720 | although sometimes there's a little bit

00:42:27.960 | of wiggle room around that age, typically after 30,

00:42:31.760 | the amount of growth hormone that's released each night

00:42:34.480 | and throughout the day is reduced by about 15%

00:42:37.360 | for every decade of life.

00:42:39.140 | As a consequence, all of the things that growth hormone does

00:42:41.720 | like encouraging higher metabolism, fat loss,

00:42:45.640 | the growth of muscle tissue, et cetera,

00:42:47.960 | is dramatically reduced as we go from 30 to 40 to 50

00:42:52.000 | and on and on.

00:42:53.240 | It's also the case that naturally released growth hormone

00:42:56.100 | tends to have positive effects on our mood

00:42:58.480 | and overall feelings of wellbeing.

00:42:59.880 | So it's also tied to our feelings of vitality

00:43:02.200 | or having feelings of energy to do things.

00:43:04.320 | And that's because growth hormone

00:43:05.680 | potently increases ATP production,

00:43:08.180 | which is involved in energy and metabolism in our cells.

00:43:11.320 | And as a consequence, our overall feelings of energy

00:43:13.920 | to just do things mental or physical.

00:43:16.320 | Now there's another hormone called IGF-1

00:43:18.480 | or insulin growth factor one,

00:43:20.320 | which is produced by the liver.

00:43:21.960 | Insulin growth factor one does many things

00:43:24.400 | similar to growth hormone,

00:43:25.920 | and it actually is released in response to growth hormone.

00:43:28.940 | So basically the way this works

00:43:30.280 | is that there's a signal that comes from the hypothalamus

00:43:32.880 | called growth hormone releasing hormone.

00:43:35.640 | And then that signal stimulates the anterior pituitary

00:43:38.640 | to release growth hormone.

00:43:40.240 | Growth hormone then is circulated throughout the blood.

00:43:43.700 | It also can access the brain itself.

00:43:46.240 | And it does different things in different tissues,

00:43:47.840 | but again, increases ATP production for energy.

00:43:50.520 | It is going to cause tissue repair in some cases.

00:43:53.360 | It's also going to encourage growth of tissues,

00:43:55.560 | not just muscles, but other tissues.

00:43:57.440 | And that's why it's involved in helping us

00:43:58.960 | achieve our full height, our full stature.

00:44:01.360 | When growth hormone reaches the liver,

00:44:02.920 | it stimulates the release of IGF-1,

00:44:05.160 | which in turn does a number of things

00:44:07.080 | that are both synergistic and different.

00:44:09.300 | That is, it works both similarly to growth hormone

00:44:11.840 | and does some things in parallel

00:44:12.940 | that are a little bit different as well.

00:44:14.480 | In particular, things related to regulation

00:44:16.860 | of blood sugar metabolism, et cetera.

00:44:18.960 | All things associated with kind of youthfulness,

00:44:21.120 | vitality, and energy.

00:44:22.700 | So it's impossible for me to say that growth hormone

00:44:24.680 | and IGF-1 do just one thing each.

00:44:26.960 | They do lots of different things

00:44:28.120 | in lots of different tissues.

00:44:29.680 | But hopefully from the description I just gave,

00:44:31.420 | you could see why some people might be interested

00:44:33.080 | in augmenting or increasing levels of growth hormone.

00:44:36.220 | Now, growth hormone has been sequenced and synthesized.

00:44:38.660 | So you can buy a synthetic version of growth hormone.

00:44:41.520 | And indeed, some people will take

00:44:43.280 | prescription growth hormone.

00:44:44.520 | They'll take this by, typically it's an injection

00:44:47.040 | that's given subcutaneously at night

00:44:49.120 | and they achieve growth of tissues,

00:44:50.600 | including muscle, et cetera.

00:44:52.080 | Keep in mind that growth hormone is indiscriminate

00:44:54.800 | with respect to which tissues it grows.

00:44:56.640 | So if you happen to have an existing tumor

00:44:59.160 | on a given body part or within a given body part,

00:45:01.660 | it will encourage growth of that tumor as well.

00:45:03.540 | That's one of the reasons some people are cautious

00:45:05.340 | about taking growth hormone.

00:45:07.120 | Another reason why many people are cautious

00:45:09.440 | about taking growth hormone is that it is subject

00:45:11.860 | to what's called negative feedback.

00:45:13.820 | If your blood levels of growth hormone are too high

00:45:17.140 | by virtue of injecting growth hormone,

00:45:19.500 | well, then the pituitary can register that

00:45:21.380 | and the brain can register that.

00:45:22.700 | And then there's a negative feedback

00:45:23.920 | that shuts down growth hormone.

00:45:25.980 | As a consequence, people have developed peptide therapeutics

00:45:28.860 | that stimulate the release of growth hormone

00:45:30.940 | and thereby the release of IGF-1,

00:45:34.100 | but not by directly stimulating the growth hormone pathway.

00:45:37.500 | Typically what these peptides are,

00:45:39.020 | are these are peptides that mimic the sorts of things

00:45:41.620 | that are typically released from the hypothalamus

00:45:43.980 | onto the pituitary and in that way,

00:45:46.300 | stimulate the release of growth hormone and downstream IGF-1.

00:45:50.260 | So what these things are typically called are secretagogues.

00:45:53.220 | These are peptide molecules that have been synthesized

00:45:55.940 | in a laboratory that stimulate the release of growth hormone

00:45:58.580 | and thereby stimulate the production of IGF-1.

00:46:01.540 | Now there are two general categories of peptides

00:46:04.100 | for stimulating the release of growth hormone.

00:46:06.980 | The first category oftentimes are referred to

00:46:09.780 | as the GHRH peptides,

00:46:11.940 | for growth hormone releasing hormone peptides.

00:46:14.920 | Now that name has certain problems

00:46:16.980 | that we'll get to in a moment,

00:46:18.280 | but let's just leave it there for the time being.

00:46:21.380 | The second category are what's called

00:46:23.080 | the growth hormone releasing peptides, right?

00:46:25.680 | Before we said growth hormone releasing hormones,

00:46:27.800 | that's the first category.

00:46:29.180 | Second ones are the growth hormone releasing peptides.

00:46:32.060 | You can already tell why this is getting confusing.

00:46:34.460 | Here's what I'm going to do.

00:46:36.020 | Rather than use that nomenclature,

00:46:37.860 | which is the typical nomenclature that's used,

00:46:40.140 | and I must say for which there's a lot of errors

00:46:42.980 | when I look out there on various YouTube videos

00:46:45.020 | and I look within even some of the reviews

00:46:47.340 | that have been written,

00:46:48.340 | people get things confused as to whether or not

00:46:50.460 | a given peptide that one would use as a therapeutic

00:46:53.580 | falls into one or the other category.

00:46:55.220 | And you'll see in a minute,

00:46:56.060 | it's a really important distinction.

00:46:57.780 | Instead, what I'm going to call these

00:46:59.380 | are category one peptides and category two peptides, okay?

00:47:04.100 | In general, category one peptides

00:47:06.020 | are going to be the ones

00:47:07.160 | that have been most thoroughly tested in humans.

00:47:09.700 | In some cases, in fact, in several cases,

00:47:11.920 | are FDA approved for certain conditions,

00:47:14.260 | and yes, are prescribed for other off-label effects.

00:47:18.940 | Again, this would be under what I'm calling

00:47:20.340 | type one growth hormone secreting peptides is sermorelin.

00:47:25.100 | Sermorelin is a synthetic compound

00:47:27.700 | designed to mimic naturally occurring

00:47:29.940 | growth hormone releasing hormone

00:47:32.340 | that is FDA approved for the treatment of short stature.

00:47:36.100 | So you can get this by prescription.

00:47:37.500 | Sometimes it comes from a compounding pharmacy.

00:47:39.580 | Other times it comes directly from Pharma

00:47:41.700 | for the name brand.

00:47:43.060 | In any case, sermorelin has been shown to mimic

00:47:45.220 | what is normally released from the hypothalamus

00:47:47.220 | and stimulates the pituitary to release growth hormone.

00:47:50.220 | And it does indeed cause increases

00:47:52.240 | in circulating growth hormone and increases in IGF-1.

00:47:56.300 | By the way, the typical dosages of sermorelin

00:47:58.220 | that are taken are anywhere from 200 to 400 micrograms.

00:48:02.220 | Typically that's done at night before sleep

00:48:04.920 | for the reasons that we talked about before.

00:48:06.940 | And typically people will take it anywhere

00:48:08.940 | from three times per week or five times per week.

00:48:11.640 | There are some disadvantages to taking it continuously

00:48:14.380 | seven days per week for long periods of time.

00:48:16.220 | There's some desensitization that can occur.

00:48:18.020 | Not much, but some can occur.

00:48:20.420 | So taken in that way,

00:48:21.460 | sermorelin has been shown to increase

00:48:23.260 | circulating levels of growth hormone and IGF-1.

00:48:26.460 | And the reason why a lot of people seek to take sermorelin

00:48:29.140 | is because they like the effects it produces.

00:48:31.340 | They like the vitality.

00:48:32.340 | They like the muscle growth.

00:48:33.340 | They like the fat loss.

00:48:34.900 | It also can increase the amount of deep sleep that you get.

00:48:38.220 | I'll just be completely forthcoming.

00:48:39.740 | I've taken sermorelin on and off

00:48:41.460 | for the last couple of years.

00:48:43.180 | I typically will take it anywhere

00:48:44.600 | from one to two nights per week.

00:48:47.260 | And I stopped taking it almost completely.

00:48:49.700 | I'll still take it every once in a great while.

00:48:52.020 | But the reason I stopped taking it

00:48:53.580 | is that I noticed that it made the sleep

00:48:55.660 | in the early part of my night very, very deep, very robust.

00:48:59.120 | But then I would wake up wide awake

00:49:00.700 | or I would sleep till morning.

00:49:02.300 | And then at least according to my eight sleep sleep tracker

00:49:05.460 | or my whoop sleep tracker,

00:49:07.300 | I wasn't getting nearly as much rapid eye movement sleep

00:49:10.400 | as I normally would.

00:49:11.580 | So at least in my case, and again, this is anecdata,

00:49:14.600 | it seemed to sort of replace rapid eye movement sleep

00:49:17.740 | with more deep sleep.

00:49:18.940 | And rapid eye movement sleep is critical

00:49:21.140 | for all sorts of things that deep sleep can't achieve

00:49:23.980 | and vice versa.

00:49:24.940 | So you really want both.

00:49:26.160 | So this is one reason why I've basically

00:49:27.980 | stopped taking sermorelin.

00:49:29.140 | I'll occasionally take it every once in a while.

00:49:31.600 | But in general, I just stopped taking it

00:49:33.700 | because whatever the positive effects might've been

00:49:36.180 | if I had taken it more consistently,

00:49:37.780 | the effects in depleting rapid eye movement sleep

00:49:40.180 | were just something I didn't want and don't want.

00:49:42.540 | And by the way, that effect on increasing deep sleep,

00:49:45.260 | that non-REM sleep is something

00:49:46.500 | that's pretty well-documented.

00:49:47.940 | The other, what I'm calling type one,

00:49:50.100 | growth hormone-promoting peptide is tesomerelin.

00:49:53.220 | This goes by the brand name Agrifta,

00:49:55.460 | and it's an FDA-approved drug for the reduction

00:49:57.640 | of visceral adiposity in HIV patients.

00:50:00.460 | So we have subcutaneous fat,

00:50:02.000 | and we have visceral fat around our organs.

00:50:03.940 | Visceral fat can be really problematic.

00:50:06.280 | And for some people who have HIV,

00:50:08.460 | or even for people who don't have HIV,

00:50:11.080 | the deposits of visceral fat can be problematic

00:50:13.660 | for their health.

00:50:14.680 | And tesomerelin, again, also called Agrifta,

00:50:17.720 | has been shown to reduce visceral adiposity.

00:50:20.360 | It also seems to produce some of the other same effects

00:50:22.740 | that sermorelin produces.

00:50:25.080 | The differences between the two relate to small differences

00:50:27.400 | in the amino acid sequence for one peptide versus the other.

00:50:30.800 | Tesomerelin is a bit more long-lasting than sermorelin,

00:50:33.760 | and therefore is taken typically about three times per week,

00:50:37.080 | not five times per week.

00:50:38.720 | Now, the third most commonly used peptide in this category

00:50:41.220 | of what I'm calling type one,

00:50:42.640 | growth hormone-secreting peptides is CJC1295.

00:50:47.000 | Gosh, I wish there was an easier name.

00:50:49.760 | CJC1295 is basically a variant

00:50:53.840 | of a different growth hormone-secreting peptide

00:50:56.380 | that was synthesized previously,

00:50:57.920 | to which they add what's called a DAC,

00:50:59.600 | a drug affinity complex.

00:51:01.080 | It's a sequence that makes it very long-lasting.

00:51:04.240 | So CJC1295 typically is only taken twice per week,

00:51:07.880 | or even once per week,

00:51:09.080 | because its effects on increasing growth hormone

00:51:11.320 | in IGF-1 last several days,

00:51:13.240 | which may sound great to you,

00:51:14.360 | especially if you're somebody that doesn't like

00:51:16.800 | taking injections, because these things in general

00:51:19.200 | have to be delivered by injection.

00:51:21.860 | But keep in mind that CJC1295 has entered clinical trials.

00:51:26.780 | There was a death within one of the clinical trials

00:51:29.440 | that was related to cardiovascular dysfunction.

00:51:32.340 | It's known to cause some fluid retention

00:51:34.640 | and increased fluid volume,

00:51:35.780 | which may have been related to that cardiovascular death.

00:51:38.280 | We don't know, okay?

00:51:39.320 | This is all kind of speculation.

00:51:41.320 | But I would say if you are somebody considering

00:51:43.760 | using a growth hormone-secreting peptide,

00:51:46.500 | the type one category is perhaps,

00:51:49.880 | and I'll give my explanation

00:51:51.280 | for why I believe this to be the case,

00:51:52.920 | perhaps the most advantageous category to explore.

00:51:56.240 | And as I mentioned before,

00:51:57.500 | you've got the options of sermorelin and tesamorelin,

00:51:59.840 | both of which are FDA approved,

00:52:01.120 | and for which there's both animal and human data.

00:52:03.400 | CJC1295, despite still being in clinical trials,

00:52:06.180 | does have this kind of stain of a death

00:52:07.800 | within the clinical trial.

00:52:09.200 | And to my mind, given that there are decent alternatives

00:52:11.760 | in sermorelin or tesamorelin,

00:52:13.540 | I don't know why anyone would specifically select CJC1295

00:52:18.540 | until all these safety issues have been resolved.

00:52:21.360 | I'd like to take a quick break

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00:52:34.680 | And that correct ratio of electrolytes

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00:53:44.400 | Okay, so there are definitely other synthetic growth hormone

00:53:47.640 | releasing hormone peptides that are out there,

00:53:50.000 | but I think these three that we've covered,

00:53:51.720 | Sermorellin, Tesomerellin, and CJC1295,

00:53:54.480 | account for the vast majority

00:53:56.160 | of those that I'd put into category one.

00:53:58.920 | The other category, which I'm going to call category two,

00:54:01.600 | you'll also hear a lot about,

00:54:03.240 | and they operate a little bit differently.

00:54:05.240 | These peptides encourage the release of growth hormone,

00:54:08.040 | but they do so either by mimicking

00:54:09.880 | or stimulating the release of another peptide

00:54:12.700 | called ghrelin.

00:54:13.800 | Some of you may be familiar with ghrelin

00:54:15.520 | because ghrelin is a peptide

00:54:16.960 | that increases in concentration when we are hungry.

00:54:20.380 | So it stimulates hunger,

00:54:21.920 | and it also stimulates anxiety somewhat.

00:54:25.120 | So you may be wondering why would anyone

00:54:26.520 | want to increase levels of growth hormone and ghrelin?

00:54:29.040 | And the reason is that the ghrelin itself

00:54:30.640 | can impact the growth hormone pathway pretty potently.

00:54:33.000 | So you can get really robust increases in growth hormone,

00:54:35.880 | but because there are ghrelin increases as well,

00:54:38.900 | you get big increases in hunger and anxiety in some people

00:54:42.080 | and lesser in others.

00:54:43.440 | Now, the different names of the peptides

00:54:44.880 | in this type two category

00:54:46.440 | are ones that you'll hear kicked around a lot these days,

00:54:48.360 | things like ipamirillin.

00:54:49.680 | Okay, so don't get ipamirillin confused with tesamirillin.

00:54:52.760 | Right, tesamirillin is a type one

00:54:54.880 | growth hormone releasing hormone peptide.

00:54:56.800 | Ipamirillin is in this category two.

00:54:59.280 | So it's definitely going to increase ghrelin,

00:55:01.280 | which is going to increase hunger.

00:55:03.420 | It does have certain advantages,

00:55:05.040 | in particular that it increases growth hormone release

00:55:07.700 | by two mechanisms.

00:55:08.800 | It increases it directly,

00:55:10.720 | and it tends to suppress something called somatostatin.

00:55:13.600 | Somatostatin is a bit of a break or an antagonist

00:55:16.360 | on growth hormone release.

00:55:18.100 | So with ipamirillin, you're essentially removing the break

00:55:20.980 | on growth hormone release,

00:55:22.020 | allowing more growth hormone to be released

00:55:23.960 | such that you get a lot of growth hormone released.

00:55:26.120 | It also tends to really improve sleep.

00:55:28.080 | But again, by increasing the amount of deep sleep,

00:55:30.640 | we don't know whether or not it does that

00:55:32.680 | at the expense of rapid eye movement sleep.

00:55:35.180 | So ipamirillin is the most commonly discussed one

00:55:37.580 | in this type two category.

00:55:39.440 | The other one that you'll hear about is called hexarellin.

00:55:42.540 | Hexarellin is available by prescription,

00:55:44.720 | and it is the strongest stimulator

00:55:46.440 | of growth hormone release,

00:55:47.560 | which leads many people to think,

00:55:48.560 | "Okay, I want hexarellin.

00:55:49.600 | That's the one that's going to give me

00:55:50.860 | the biggest growth hormone pulse."

00:55:52.680 | And indeed the growth hormone pulses from hexarellin

00:55:55.260 | can be as great as two or three times more

00:55:57.600 | than with the other growth hormone secreting peptides

00:56:00.120 | that we've talked about.

00:56:01.160 | However, we know that hexarellin

00:56:03.280 | can also dramatically increase prolactin,

00:56:06.140 | which can cause suppression of libido.

00:56:08.480 | It can cause fluid retention.

00:56:09.800 | It can cause a kind of feeling of malaise,

00:56:11.920 | especially at high levels.

00:56:13.480 | And perhaps most problematically,

00:56:15.120 | hexarellin can desensitize the receptors

00:56:18.600 | for growth hormone-releasing hormone,

00:56:20.760 | such that your system will no longer respond

00:56:23.320 | either to the hexarellin or to any other peptide,

00:56:26.000 | or perhaps most importantly, to any endogenous,

00:56:28.720 | that is naturally made growth hormone, excuse me,

00:56:31.520 | releasing hormone that you would make, okay?

00:56:33.680 | So that's something to really consider.

00:56:35.080 | If you're going to explore hexarellin,

00:56:36.460 | make sure, please, that you're working with a physician.

00:56:39.220 | Make sure that you're not taking too much of it

00:56:40.860 | or for too long, and keep an eye on those prolactin levels

00:56:44.160 | because those can be problematic if they get too high.

00:56:46.980 | And, you know, by my read,

00:56:48.940 | I can't see why anyone would use high doses of hexarellin,

00:56:51.580 | maybe low doses of hexarellin,

00:56:53.300 | if your doctor thinks that's what's appropriate for you,

00:56:55.340 | but you'd really want to avoid that receptor desensitization

00:56:58.620 | because you could essentially

00:56:59.460 | turn off the system permanently.

00:57:01.420 | Now, there are a bunch of other,

00:57:02.340 | what I'm calling type two growth hormone promoting peptides.

00:57:06.940 | These include GHRP-2, GHRP-3, GHRP-6.

00:57:11.540 | Again, different amino acid sequences,

00:57:13.400 | all designed to achieve the same thing,

00:57:14.940 | which is more growth hormone.

00:57:16.300 | Things like GHRP-3 can potently increase growth hormone,

00:57:20.140 | but are known to also potently increase prolactin

00:57:22.780 | and cortisol, leading to more than a doubling

00:57:25.300 | of circulating cortisol,

00:57:26.840 | which, depending on how well-regulated it is

00:57:29.620 | across the time of day, can be problematic.

00:57:32.000 | In other words, you want cortisol levels pretty high

00:57:34.460 | in the early part of the day,

00:57:35.340 | but you want them very, very low

00:57:36.780 | in the later part of the day and at night.

00:57:38.380 | And keep in mind that almost always,

00:57:40.420 | these growth hormone peptides,

00:57:41.940 | whether or not they're type one or type two peptides,

00:57:45.680 | are taken before bed,

00:57:47.540 | typically, you know, 20 or 30 minutes before sleep.

00:57:50.460 | Always, it's suggested that they be taken

00:57:53.140 | at least an hour and a half after eating any food

00:57:55.860 | and that you don't eat for at least 30 minutes afterwards,

00:57:58.420 | because if you happen to have elevated blood sugar

00:58:00.980 | or you've got food in your gut,

00:58:02.120 | they're not going to have as potent an effect

00:58:04.640 | at increasing growth hormone and IGF-1.

00:58:07.760 | So again, you want to avoid food in the hour and a half,

00:58:10.560 | probably two hours before taking them,

00:58:12.280 | and certainly in the half hour or longer after,

00:58:15.320 | which is why most people take them right before going

00:58:16.960 | to sleep and add or augment that big growth hormone pulse

00:58:19.960 | that occurs in the early part of the night.

00:58:22.280 | And then many people have perhaps heard

00:58:23.760 | of what's called MK-677,

00:58:26.080 | which is simply an oral version, a non-injectable,

00:58:28.600 | but oral version of these GHRPs.

00:58:32.280 | And it tends to have the same issues

00:58:34.460 | that the other GHRPs have, which are elevated cortisol,

00:58:37.340 | and in some cases, elevated prolactin as well.

00:58:39.740 | Okay, so if we just kind of zoom out from all this,

00:58:42.140 | we can say that yes, indeed, there are synthetic peptides

00:58:45.140 | that can potently increase growth hormone and IGF-1.

00:58:47.700 | I explained the rationale for why people would want that

00:58:51.540 | or perhaps to explore that.

00:58:53.380 | I'm certainly not suggesting anyone do this.

00:58:55.900 | Again, I am suggesting that if you do explore it,

00:58:58.260 | you work with a board-certified physician

00:59:00.360 | and that you get these compounds

00:59:02.920 | from a quality compounding pharmacy

00:59:04.720 | or by their name brand prescription.

00:59:07.320 | In type one, we've got sermorelin and tesamorelin.

00:59:09.980 | Both are FDA approved.

00:59:12.360 | For certain purposes, they're being used off-label

00:59:14.160 | for increasing growth hormone and IGF-1

00:59:16.180 | for the sorts of things we're talking about here.

00:59:19.040 | They are taken anywhere from three times per week

00:59:21.180 | to five times per week.

00:59:22.400 | Keep in mind, tesamorelin lasts a little bit longer

00:59:25.080 | than sermorelin.

00:59:26.620 | CJC 1295 is the third in that category

00:59:30.140 | of type one growth hormone secreting peptides,

00:59:33.100 | but it may, again, may, we don't know,

00:59:35.720 | have some safety issues that still need to be resolved,

00:59:38.080 | making sermorelin and tesamorelin, at least to my mind,

00:59:40.740 | better options should you decide to go down this path.

00:59:43.700 | The type two growth hormone releasing peptides

00:59:45.880 | include things like hexarellin,

00:59:47.400 | which are very potent at increasing growth hormone,

00:59:49.160 | but can potentially increase other things as well.

00:59:52.360 | But of more concern is really that it can cause

00:59:55.240 | receptor desensitization,

00:59:56.600 | maybe even turn off the whole receptor pathway.

00:59:58.340 | That would not be good.

00:59:59.240 | Ipermorelin, again, increases growth hormone directly

01:00:01.640 | and allows more of it to be released

01:00:03.560 | by suppressing its break, its natural break,

01:00:05.720 | which is the somatostatin.

01:00:07.000 | And then the GHRP-2, 3, 6, and MK-677,

01:00:11.360 | all of which can potently increase growth hormone,

01:00:14.520 | need to be considered in light of the fact

01:00:16.500 | that they cause big increases in cortisol,

01:00:19.100 | and in some cases can cause some receptor internalization

01:00:21.800 | or desensitization as well,

01:00:23.520 | although not as potently as hexarellin.

01:00:25.620 | So hopefully that description clarifies

01:00:27.200 | some of what you've heard out there

01:00:29.200 | about these different compounds

01:00:30.640 | and their different names, et cetera.

01:00:31.960 | It can be very confusing.

01:00:33.200 | I did take the liberty of designating a type one

01:00:35.520 | and a type two category.

01:00:36.920 | I did that for sake of clarity

01:00:38.140 | because there are a lot of different acronyms and numbers,

01:00:40.040 | et cetera, that can be really confusing to people.

01:00:41.920 | And I hope that that will be useful

01:00:43.440 | in facilitating further discussions

01:00:45.400 | about these compounds going forward.

01:00:47.700 | Two additional brief, but important points.

01:00:50.240 | Many of the peptide vendors that are out there

01:00:53.040 | and physicians that are working with peptides

01:00:55.200 | will combine different growth hormone-promoting peptides.

01:00:59.340 | So they'll, for instance, have sermorellin or tesomerellin

01:01:02.800 | in combination with hexarellin,

01:01:05.520 | or they'll use ipermorellin in combination with CJC-1295.

01:01:09.760 | While I'm not opposed to that approach,

01:01:11.980 | you just want to make sure that the dosing,

01:01:14.080 | or I should say the relative dosing of each peptide

01:01:17.140 | is such that you're avoiding unnecessary increases

01:01:21.880 | in prolactin and cortisol,

01:01:23.440 | and that you're not hitting a pathway redundantly.

01:01:25.860 | That's actually the logic of combining different things.

01:01:27.920 | These different amino acid sequences,

01:01:30.040 | these different peptides that is,

01:01:31.560 | are designed to stimulate different modes of action

01:01:35.080 | for the same peptide.

01:01:36.680 | So the naturally occurring peptide

01:01:38.220 | goes and does a bunch of things, those pleiotropic effects.

01:01:40.560 | And these different peptides

01:01:41.800 | that are of different amino acid sequences

01:01:43.500 | are designed to reduce visceral adiposity a bit more,

01:01:47.600 | or promote deep sleep a bit more,

01:01:49.300 | or to promote muscle growth a bit more.

01:01:51.240 | So when people are combining different things in cocktail,

01:01:54.040 | it's not necessarily a bad thing,

01:01:55.480 | but you want to make sure that you're working with someone

01:01:56.880 | who's very familiar with peptides,

01:01:59.080 | you know, really has been in the peptide space

01:02:00.640 | for a long time and understands how these things work alone

01:02:03.280 | and in combination.

01:02:04.400 | And there are some excellent physicians that are doing that.

01:02:08.440 | And we plan to have at least one of them

01:02:10.520 | on the Huberman Lab podcast as a guest

01:02:12.680 | in the not too distant future.

01:02:13.840 | And you can bet that this conversation

01:02:15.720 | will facilitate your understanding of that discussion.

01:02:18.200 | The second point is that there are, of course,

01:02:20.380 | risks to taking anything,

01:02:22.640 | but in particular to exploring augmentation

01:02:25.680 | of the growth hormone pathway.

01:02:27.600 | When people take growth hormone itself,

01:02:30.060 | there are common risks such as carpal tunnel syndrome.

01:02:32.840 | That has to do in part with the fact

01:02:34.420 | that it can potently increase cartilage growth.

01:02:37.520 | There can be active changes in the structure

01:02:40.240 | of one's head and face and body.

01:02:42.040 | There's a so-called lean but distended gut.

01:02:45.400 | So people that aren't carrying a lot of subcutaneous fat,

01:02:48.340 | but that the gut becomes extended.

01:02:50.880 | Sometimes you can get changes in the face,

01:02:52.480 | like the kind of a thickening of the bone above the brow.

01:02:57.480 | You'll see that.

01:02:58.560 | And sometimes people will look quite different

01:03:00.320 | after taking growth hormone for a series of time

01:03:02.400 | than they did before.

01:03:03.320 | It can really change one's stature

01:03:04.880 | and shape to a considerable degree.

01:03:07.960 | It also can create a kind of a skin texture

01:03:12.960 | that is a little bit unnatural or unusual.

01:03:14.980 | You sometimes can see this

01:03:15.920 | in people that take a lot of growth hormone.

01:03:18.080 | In general, when people take growth hormone

01:03:20.140 | promoting peptides,

01:03:21.500 | the changes in body structure are not as dramatic

01:03:24.400 | as when people take growth hormone itself.

01:03:26.440 | But body shape changes and cosmetic changes aside,

01:03:29.680 | keep in mind that anytime we augment growth hormone,

01:03:33.040 | either by taking growth hormone directly

01:03:35.320 | as a synthetic compound,

01:03:37.160 | or by taking a peptide that increases the amount

01:03:40.440 | of growth hormone that we release,

01:03:42.280 | we are increasing our tumor growth risk and our cancer risk.

01:03:46.000 | And that's because growth hormone and IGF-1

01:03:49.080 | are somewhat indiscriminate in terms of the tissues

01:03:52.880 | that they promote the growth of.

01:03:54.500 | So if you have a tumor someplace and it's small,

01:03:56.680 | taking exogenous growth hormone

01:03:58.760 | or increasing the amount of growth hormone that you release

01:04:01.280 | by taking one of these peptides that we discussed

01:04:03.560 | will increase the size of that tumor.

01:04:05.520 | It's very likely.

01:04:06.520 | And you can imagine that if you're taking a peptide

01:04:08.380 | to increase growth hormone

01:04:09.400 | and you're taking something like BPC-157,

01:04:11.560 | something that a lot of people are starting to do nowadays,

01:04:15.000 | you could potentially increase both the size

01:04:17.600 | and the vascularization of a given tumor.

01:04:20.320 | So just keep that in mind,

01:04:21.400 | just as there are anti-cancer drugs

01:04:23.500 | that focus on the VEGF pathway

01:04:25.020 | to try and discourage vascularization of tumors,

01:04:28.660 | there are drugs that discourage the release

01:04:30.440 | of growth hormone to discourage the growth of tumors.

01:04:33.560 | So if you're listening to this, you might be thinking,

01:04:35.240 | well, why in the world would anybody take this stuff?

01:04:37.220 | Well, people like the effects

01:04:38.780 | of having elevated growth hormone.

01:04:40.140 | They like the effects of recovering

01:04:42.320 | from an injury more quickly,

01:04:43.480 | but there's always going to be a trade-off

01:04:45.300 | between potential benefit and potential risk.

01:04:47.940 | The one thing that we can say

01:04:49.480 | for these growth hormone secretogogues,

01:04:52.040 | sermorelin, tesamorelin in particular,

01:04:54.700 | is that they are FDA approved as compounds.

01:04:56.960 | However, they are not approved for all the purposes

01:04:59.020 | that people are taking them for,

01:05:00.080 | such as cosmetic effects, et cetera.

01:05:02.060 | So I'm certainly not being disparaging of people

01:05:03.960 | that decide to make the choice to take these compounds.

01:05:06.600 | That's your right entirely.

01:05:08.920 | But I do think that you should be informed

01:05:10.920 | about the potential risks.

01:05:12.080 | And if you are somebody who's considering

01:05:13.440 | taking any of these compounds,

01:05:14.960 | there are certain considerations

01:05:16.080 | that you definitely should pay attention to.

01:05:17.740 | So for instance, how old are you?

01:05:19.640 | If you're younger than 30,

01:05:20.720 | I don't know why you'd want to augment growth hormone

01:05:22.580 | unless you and your doctor decide

01:05:23.760 | that there's a clinical need

01:05:24.920 | or some other urgent need to do so,

01:05:27.720 | because you're already making a lot of growth hormone.

01:05:29.800 | If you're older than 30

01:05:31.000 | and you're interested in using these compounds,

01:05:32.720 | to me, it stands to reason that,

01:05:34.920 | of course, you want to make sure

01:05:36.120 | that you don't have any tumors or cancers

01:05:37.880 | that you could potentially exacerbate.

01:05:40.020 | But in addition to that,

01:05:41.360 | that you really think about

01:05:42.400 | using the minimal effective dose

01:05:44.000 | and that you use perhaps even the mildest

01:05:46.120 | of these different compounds

01:05:47.480 | in order to make sure that you don't desensitize

01:05:49.640 | any of the receptor pathways.

01:05:51.120 | And of course, there is no reason

01:05:53.200 | why anyone should use these compounds

01:05:54.640 | unless they absolutely feel they need to,

01:05:56.520 | and there's a potential benefit there.

01:05:57.980 | I personally, as I mentioned before,

01:05:59.640 | tried sermorelin for a short while.

01:06:01.640 | The reductions in rapid eye movement sleep

01:06:03.500 | were problematic enough for me

01:06:04.700 | that I decided to just not take it.

01:06:06.580 | And it's not something that I've returned to

01:06:07.920 | except every once in a great while,

01:06:09.560 | I might do it to augment deep sleep just a little bit.

01:06:12.080 | The next category of peptide effects

01:06:13.760 | that we're going to discuss

01:06:15.120 | are peptides involved in longevity.

01:06:17.360 | And this is actually going to be a pretty quick discussion

01:06:19.660 | because really the main one in this category,

01:06:22.360 | besides thymosin beta-4,

01:06:24.000 | remember thymosin beta-4 we talked about earlier,

01:06:26.360 | this is a peptide that's naturally released from the thymus

01:06:29.040 | and the thymus is a structure that depletes over time

01:06:32.000 | as children age.

01:06:33.280 | So some people will take thymosin beta-4

01:06:35.160 | as kind of a longevity agent,

01:06:36.800 | hoping that it will increase repair of tissues,

01:06:39.840 | recovery from exercise, et cetera,

01:06:41.740 | but it's not really aimed at longevity per se.

01:06:44.240 | It's really aimed at replacing something

01:06:45.820 | that's present in youth

01:06:46.760 | and then tends to dissipate as we get older,

01:06:48.520 | that is the thymus and related peptides from the thymus.

01:06:51.680 | But the big one in the category of peptides

01:06:53.640 | to potentially, I want to highlight,

01:06:55.080 | potentially improve longevity is epitalin.

01:06:59.820 | Epitalin is also sometimes spelled and pronounced epithalin.

01:07:03.720 | Okay, don't ask me why.

01:07:05.280 | And as with BPC-157,

01:07:07.340 | there are quite a few animal studies exploring epithalin

01:07:10.340 | and its effects on various tissues,

01:07:11.840 | as well as the naturally occurring peptide

01:07:14.680 | that it's meant to resemble.

01:07:16.920 | Epithalin is a peptide that's secreted

01:07:18.960 | from the pineal gland.

01:07:20.640 | The pineal gland is a gland that most people associate

01:07:23.700 | with melatonin release,

01:07:24.900 | and that's because the cells within the pineal,

01:07:27.080 | called pinealocytes, secrete melatonin at night.

01:07:31.920 | It's what makes us feel sleepy and go to sleep.

01:07:35.280 | Melatonin is suppressed by light viewed by the eyes.

01:07:38.080 | There's actually a pathway that goes from the eyes

01:07:39.920 | into the brain.

01:07:40.760 | There are a couple of stages.

01:07:41.580 | They go up through the cervical ganglion

01:07:42.880 | from the brainstem and up to the pineal

01:07:44.600 | and suppress melatonin release.

01:07:47.160 | Now, the pineal makes other things besides melatonin.

01:07:49.760 | It also makes a peptide called epithalamin.

01:07:52.560 | Epithalamin is a peptide that is naturally released

01:07:55.560 | from the pineal, especially early in life,

01:07:57.720 | and that's associated with various anti-inflammatory effects

01:08:01.200 | on other cells and tissues in the body.

01:08:03.600 | And it does appear to be able to adjust telomere length,

01:08:07.280 | which is a feature of cells that's thought to be associated

01:08:09.820 | with the longevity of cells or how long they live.

01:08:12.620 | Keep in mind that the relationship between telomeres

01:08:14.980 | and longevity is a controversial one.

01:08:17.040 | People were very excited about this some years back.

01:08:19.540 | Then people batted down that idea,

01:08:21.600 | showing that telomere length was not associated

01:08:24.200 | with longevity, especially in humans.

01:08:25.840 | And now it's sort of a back and forth within the field.

01:08:28.960 | Keep in mind that epitalin, again,

01:08:31.160 | also sometimes written and pronounced epithalin,

01:08:34.040 | is designed to mimic this naturally occurring

01:08:36.440 | peptide epithalamin, okay?

01:08:39.060 | So the nomenclature can get a little bit confusing.

01:08:41.920 | And what you'll find is that epitalin is available

01:08:44.660 | as a synthetic compound.

01:08:46.080 | It can be obtained in clean form from compounding pharmacies.

01:08:49.920 | And a good number of people will use it

01:08:52.560 | as a longevity agent based largely on animal data

01:08:56.040 | that it can suppress tumor growth.

01:08:58.340 | It can increase telomere length.

01:09:00.300 | And to some extent that it can recalibrate

01:09:02.840 | the circadian rhythm changes and the disruptions

01:09:06.640 | in the patterns of melatonin that occur as animals

01:09:09.920 | and perhaps as humans age.

01:09:11.920 | This is an important point.

01:09:13.000 | The pineal gland, despite being very, very small,

01:09:15.520 | about the size of a pea and sitting kind of in the mid area

01:09:18.920 | of the brain for you aficionados,

01:09:20.520 | it sits kind of like right on the roof of the diencephalon.

01:09:23.800 | And what it does is it will release melatonin each night

01:09:27.320 | in darkness, it can release epithalamin.

01:09:31.960 | And at those times, it can go and have these myriad effects

01:09:35.360 | on restoring the brain and body during sleep.

01:09:38.540 | There are other things that occur during sleep

01:09:39.900 | that are essential, but those are key components

01:09:42.440 | of the restorative features of sleep.

01:09:44.260 | Now we know that as we age, the amount of melatonin

01:09:47.440 | that we release is decreased such that if you look in babies

01:09:51.860 | and teens, et cetera, melatonin levels are very, very high

01:09:55.140 | compared to people of middle age and of elderly age.

01:09:58.700 | Likewise, epithalamin levels decrease with time.

01:10:02.180 | And as a consequence, markers of tissue inflammation

01:10:05.020 | also increase as we age 'cause you're sort of removing

01:10:07.940 | this anti-inflammatory compound that's released each night.

01:10:11.220 | Now there are a bunch of theories

01:10:12.260 | as to why the pineal regresses with age.

01:10:14.980 | There's some kind of wild ones about fluoride

01:10:17.380 | and a depletion of the pineal.

01:10:19.500 | I'll do a whole episode on the pineal at some point

01:10:21.320 | and we'll explore that.

01:10:22.500 | Some of them are very niche.

01:10:23.660 | Some of them are frankly completely false

01:10:25.780 | and others have some merit and are starting

01:10:27.700 | to gain some data within the standard scientific community.

01:10:31.960 | The overall point here about peptides for longevity

01:10:34.140 | can be summarized very easily.

01:10:36.020 | The logic is just as we have a thymus early in life,

01:10:39.420 | the thymus secretes certain things

01:10:41.300 | and those things seem to accelerate

01:10:44.660 | robust tissue healing early in life.

01:10:46.980 | And as the thymus disappears,

01:10:48.300 | tissue healing gets less robust.

01:10:50.300 | That's the logic for taking things like thymus

01:10:51.940 | and beta-4, TB 500.

01:10:54.220 | So too, we have a tissue, the pineal,

01:10:57.300 | that secretes certain things early in life

01:10:59.660 | that are associated with lots of deep sleep

01:11:01.860 | and robust tissue repair and long cellular life.

01:11:06.540 | The logic then is by taking epitalin,

01:11:09.020 | you can mimic this peptide that's normally released

01:11:11.860 | from a nice, young, healthy pineal.

01:11:14.180 | And in that sense, encourage anti-inflammation pathways

01:11:18.300 | as well as cellular longevity pathways.

01:11:21.200 | That's the basic idea.

01:11:22.700 | And again, it rests largely on the animal data for which,

01:11:25.700 | yes, there's some interesting studies

01:11:27.340 | showing suppression of age-related ocular diseases.

01:11:31.140 | There's some nice studies showing telomere expansion.

01:11:34.260 | There's some nice studies showing

01:11:35.340 | that several features of brain aging and body aging

01:11:38.380 | can indeed be partially offset

01:11:40.700 | by things like epitalin peptides.

01:11:43.080 | But it is indeed a leap that people are taking

01:11:46.160 | when they are deciding or taking epitalin

01:11:49.580 | in order to extend their life, right?

01:11:51.140 | It's the logic is all there,

01:11:52.960 | but the pieces are sort of kludged together

01:11:54.740 | between what we know about the animal studies,

01:11:56.660 | what we know about the naturally occurring compounds

01:11:59.260 | that these peptides are designed to mimic.

01:12:01.580 | And yet there are still no clinical trials

01:12:03.480 | that point directly to taking X amount of epitalin

01:12:06.680 | several times per week as a way to extend life.

01:12:09.180 | The fourth and final category of peptide effects

01:12:11.620 | that we're going to talk about are effects on vitality,

01:12:14.900 | both mood and libido.

01:12:16.660 | And really the main players within this category of peptides

01:12:20.580 | are the so-called

01:12:21.620 | melanocyte-stimulating hormone-related peptides, okay?

01:12:25.680 | Just to give you a little bit of background,

01:12:27.420 | remember the pituitary?

01:12:28.940 | The pituitary gland,

01:12:29.980 | that stalk that extends out of the brain

01:12:32.060 | and can release growth hormone from the anterior pituitary?

01:12:35.500 | Well, it's got a middle segment or a medial segment,

01:12:38.060 | and there's a hormone that's released from there

01:12:40.740 | called melanocyte-stimulating hormone.

01:12:43.420 | Melanocyte-stimulating hormone

01:12:44.820 | has the effect of stimulating pigmentation of the skin

01:12:47.540 | by activating what are called melanocytes

01:12:49.480 | that exist within the skin.

01:12:51.280 | So the peptides, melanotan-1, melanotan-2,

01:12:54.700 | melanotan-3, melanotan-4, melanotan-5,

01:12:57.180 | because there are five of them,

01:12:58.300 | are different peptides,

01:12:59.460 | that is peptides with different amino acid sequences,

01:13:02.480 | all of which mimic naturally occurring

01:13:04.380 | melanocyte-stimulating hormone,

01:13:06.620 | but that act preferentially on one set of melanocyte-stimulating

01:13:10.060 | hormone receptors or another

01:13:11.540 | in order to get different effects.

01:13:13.500 | So let's back up a little bit

01:13:15.600 | and talk about the melanocortin system, right?

01:13:18.140 | The melanocortin system is a system whereby viewing light

01:13:22.120 | or getting light on the skin,

01:13:24.240 | typically ultraviolet light of the ultraviolet B type,

01:13:28.220 | okay, there's two different types of ultraviolet light,

01:13:30.260 | but basically sunlight is what the system evolved

01:13:33.220 | to respond to,

01:13:34.140 | shown to the eyes and/or to the skin,

01:13:38.020 | stimulates the melanocortin system.

01:13:39.780 | It goes from the eyes to the hypothalamus,

01:13:43.300 | from the hypothalamus to the pituitary,

01:13:45.820 | and then the melanocyte-stimulating hormone

01:13:47.980 | is then released into the bloodstream,

01:13:49.700 | can travel to the melanocytes

01:13:51.780 | and cause pigmentation of the skin.

01:13:53.740 | This is what is responsible for tanning.

01:13:56.020 | There's also a pathway whereby the light stimulates

01:13:58.360 | the melanocyte-stimulating hormone system,

01:14:00.340 | and in parallel, it stimulates the release of dopamine.

01:14:03.340 | Now, for any of you that have lived

01:14:04.740 | in a part of the world in which it's very, very dark

01:14:07.140 | with very short days in the winter

01:14:09.140 | and longer days and a lot of sunlight during the summer,

01:14:11.980 | you're probably familiar with the fact

01:14:14.060 | that when the sun comes out, people start feeling better.

01:14:16.580 | They have more energy, they're more motivated.

01:14:18.460 | A number of different systems related to mood and libido

01:14:21.020 | tend to increase.

01:14:22.700 | This is the consequence of sunlight

01:14:24.860 | activating the melanocorticoid system.

01:14:27.420 | And by the way, this system is very active

01:14:29.220 | in other animals as well,

01:14:31.420 | animals that are white

01:14:32.980 | or tend to be a pale color during the winter.

01:14:35.400 | Then as spring arrives,

01:14:37.060 | the sunlight stimulates this very same system

01:14:39.900 | and leads to darkening of the pelage,

01:14:41.520 | so their hair goes from white or gray to brown

01:14:45.220 | or even dark black or some combination of those.

01:14:48.000 | And in combination, dopamine is increased,

01:14:50.020 | libido is increased,

01:14:50.860 | and the animals start breeding

01:14:51.960 | in the spring and summer months.

01:14:53.380 | Okay, so this is a well-conserved system across species,

01:14:56.100 | and it exists to some extent in us as well.

01:14:58.940 | So there are essentially five different synthetic peptides

01:15:02.940 | called melanotan 1, 2, 3, 4, and 5,

01:15:05.240 | each of which is designed to mimic

01:15:08.020 | melanocyte-simulating hormone,

01:15:10.020 | but each of which activates different receptors

01:15:12.320 | to different degrees,

01:15:13.840 | and some can cross the blood-brain barrier and some can't.

01:15:16.620 | And as a consequence,

01:15:17.460 | some impact mood and libido and others don't.

01:15:21.100 | The simple way to look at this is that melanotan 1

01:15:23.420 | does not cross the blood-brain barrier.

01:15:25.860 | It does, however, stimulate the melanocytes of the skin,

01:15:28.540 | so it leads to tanning or darkening of the skin.

01:15:30.940 | Melanotan 2, 3, 4, and 5

01:15:34.860 | also lead to darkening of the skin

01:15:36.380 | by way of activating melanocytes in the skin,

01:15:39.660 | but because they can cross the blood-brain barrier,

01:15:42.340 | they cause effects that are at the level of psychology,

01:15:46.640 | really, and at the level of appetite

01:15:49.000 | and things of that sort.

01:15:49.940 | In general, the pattern is to increase mood and libido

01:15:52.920 | and to decrease appetite.

01:15:54.360 | Things that are associated with the transition

01:15:55.980 | from winter to spring and summer months

01:15:58.120 | in humans and in other animals.

01:16:00.060 | Now, one of the things about the peptide literature

01:16:02.960 | is that it loves acronyms and numbers,

01:16:05.680 | and so there's a peptide, PT-141,

01:16:08.860 | that falls into this category

01:16:11.280 | of activating the melanocorticoid system.

01:16:15.300 | And PT-141 is also known as the prescription drug, Vilese.

01:16:20.220 | PT-141, or Vilese, is FDA-approved

01:16:23.400 | for the treatment of premenopausal hypoactive sexual desire.

01:16:27.640 | So this is FDA-approved for the treatment of women

01:16:29.960 | that have suppressed libido.

01:16:32.000 | However, men also will take Vilese

01:16:35.600 | for hypoactive sexual desire.

01:16:38.500 | This is obviously prescribed off-label by physicians,

01:16:41.680 | but keep in mind, as with the other peptides

01:16:43.560 | in this pathway, Vilese will stimulate pigmentation.

01:16:47.400 | So whether or not you consider that a side effect

01:16:49.560 | or a benefit depends on, I guess,

01:16:51.060 | your baseline level of pigmentation

01:16:52.480 | and how much level of pigmentation you actually want.

01:16:55.240 | Now, there are some side effects

01:16:56.360 | associated with these compounds.

01:16:58.360 | One of the more common ones is nausea,

01:17:00.800 | and that's because there are melanocytes

01:17:02.160 | simulating hormone receptors all throughout the gut.

01:17:06.560 | They can also cause flushing of the skin,

01:17:09.060 | and they can cause blood pressure to increase.

01:17:12.660 | Also, folks with melanoma should be very cautious

01:17:15.660 | about using any of the peptides that stimulate melanocytes

01:17:18.600 | because that could potentially exacerbate melanoma.

01:17:21.580 | The next peptide in this category,

01:17:23.020 | peptides for vitality and libido, is kispeptin.

01:17:26.820 | Kispeptin is a peptide that wasn't discovered that long ago.

01:17:30.100 | I actually can recall when the first papers

01:17:31.500 | about kispeptin came out.

01:17:33.220 | And basically, kispeptin is a peptide

01:17:36.220 | that is naturally made within the brain,

01:17:38.200 | and it's upstream of some of the hypothalamic signals

01:17:41.920 | that activate the pituitary

01:17:43.520 | for sake of hormone production and reproduction.

01:17:47.680 | So I'll just walk you through this pathway.

01:17:49.240 | It's actually quite simple.

01:17:50.800 | You've got the pituitary.

01:17:51.800 | You're now familiar with the pituitary.

01:17:53.200 | And the pituitary releases two different hormones

01:17:55.280 | in both males and females.

01:17:56.260 | It releases luteinizing hormone,

01:17:58.320 | and it releases follicle-stimulating hormone.

01:18:00.880 | If you watched the episodes

01:18:02.000 | that we did about testosterone and estrogen,

01:18:04.300 | if you watched the episode that I did

01:18:05.840 | on male and female fertility,

01:18:07.600 | if you watched the episode that I did

01:18:09.180 | with Dr. Michael Eisenberg from Stanford

01:18:11.280 | or Dr. Natalie Crawford,

01:18:12.560 | who's an OBGYN specializing in fertility,

01:18:15.400 | we talked a lot about LH and FSH.

01:18:18.240 | Basically, FSH, as the name suggests,

01:18:20.980 | stimulates the growth of the follicle,

01:18:22.640 | the egg in the female,

01:18:24.120 | and it stimulates sperm production in males.

01:18:26.840 | Luteinizing hormone stimulates testosterone production

01:18:29.720 | from the gonad in males,

01:18:31.040 | and it also stimulates estrogen production

01:18:34.620 | and to some extent,

01:18:35.460 | testosterone production in females as well.

01:18:37.900 | So we need LH and FSH to stimulate the gonads,

01:18:41.140 | the ovary or the testes.

01:18:44.200 | The hormone that stimulates LH and FSH release

01:18:47.440 | is called GNRH or gonadotropin-releasing hormone,

01:18:51.180 | and it comes from the hypothalamus.

01:18:53.500 | So GNRH is a signal that promotes LH and FSH release.

01:18:57.980 | Now that raises the question, what turns on GNRH?

01:19:00.780 | And the signal that turns on GNRH is cispeptin.

01:19:03.980 | Cispeptin, in other words,

01:19:05.160 | is further upstream from GNRH and LSH and FSH.

01:19:08.940 | It's a cascade.

01:19:09.780 | It goes cispeptin, GNRH, LH, FSH, testosterone, estrogen.

01:19:14.540 | Okay, that's the pathway.

01:19:16.340 | Now, it's very clear that cispeptin is involved

01:19:19.260 | in the activation of puberty,

01:19:21.120 | the transition from pre-pubertal

01:19:23.100 | to post-pubertal stages of life.

01:19:25.940 | It's also involved in any of the sort of downstream effects

01:19:29.900 | of having elevated LH and FSH, including elevated vitality,

01:19:33.980 | which includes both energy and in some cases, libido.

01:19:37.340 | So there's naturally occurring cispeptin,

01:19:39.940 | and there's now synthetically generated cispeptin

01:19:43.140 | designed to mimic naturally occurring cispeptin,

01:19:45.540 | and it's actually prescribed

01:19:47.340 | for what's called hypothalamic amenorrhea.

01:19:50.540 | Hypothalamic amenorrhea is the loss

01:19:53.020 | or the absence of periods of menstrual cycles

01:19:56.060 | that are the consequence of deficits

01:19:58.720 | within the hypothalamus itself.

01:20:00.500 | So not something within the ovary

01:20:01.860 | or a lack of the pituitary to make LH or FSH,

01:20:05.020 | but a deficit of the hypothalamus to promote LH and FSH

01:20:09.100 | and the downstream hormones, testosterone and estrogen.

01:20:12.340 | Incidentally, there are also cispeptin antagonists, okay,

01:20:15.740 | drugs that are designed to suppress cispeptin,

01:20:18.180 | and those are used to treat some of the symptoms

01:20:20.220 | of menopause, including night sweats

01:20:21.900 | and some of the, what are called vasomotor symptoms.

01:20:24.480 | So cispeptin is obviously a key player

01:20:26.700 | in this whole pathway of steroid hormone release,

01:20:29.560 | the steroid hormones being testosterone and estrogen.

01:20:31.560 | There are other steroid hormones as well, of course.

01:20:33.880 | Now, there are folks within the landscape

01:20:35.280 | of peptide therapeutics,

01:20:36.360 | folks meaning physicians and other practitioners,

01:20:39.080 | who said, "Ah, well, here's a peptide

01:20:41.080 | "that is known to promote all these hormone pathways

01:20:43.340 | "that are associated with vitality, libido, et cetera."

01:20:46.080 | And so there are people who take cispeptin peptides

01:20:49.480 | as a way to stimulate these pathways,

01:20:51.800 | and they're doing so for the specific purpose

01:20:54.400 | of increasing vitality as it relates to libido and mood,

01:20:57.820 | and to get the downstream increases

01:20:59.980 | on testosterone and estrogen.

01:21:01.620 | And of course, some people are taking cispeptin peptides

01:21:03.820 | to treat hypothalamic amenorrhea.

01:21:05.900 | And as I mentioned,

01:21:06.740 | some people are taking cispeptin antagonists.

01:21:08.840 | They're trying to block the cispeptin pathway

01:21:11.040 | in order to reduce some of the vasomotor

01:21:13.140 | and other symptoms of menopause.

01:21:15.140 | I will say, despite the fact

01:21:16.180 | that the cispeptin pathway is well-known,

01:21:18.060 | and despite the fact that the cispeptin peptide

01:21:20.500 | is designed to mimic a naturally occurring peptide

01:21:22.660 | that has a pretty constrained set of functions

01:21:25.420 | in the hypothalamic pituitary system,

01:21:28.980 | and their downstream effects on the gonads,

01:21:31.980 | the use of cispeptin to increase vitality and libido

01:21:34.700 | is a bit of a, let's just say,

01:21:37.060 | it's a little bit of a wild card.

01:21:38.820 | We don't yet know all the effects of cispeptin.

01:21:41.620 | Again, it was fairly recently discovered.

01:21:43.740 | We have it in mind that it's involved in these pathways,

01:21:46.300 | but I should say, every time we look at a given peptide,

01:21:48.300 | whether or not it's ghrelin, or hypocretin orexin,

01:21:50.960 | or it's GLP-1, what we find is that, again,

01:21:54.780 | there are these pleiotropic effects.

01:21:56.700 | There is rarely, if ever, one specific effect,

01:22:00.020 | and it's not just a concern about side effects

01:22:01.980 | that we want to take these pleiotropic effects

01:22:03.620 | into consideration.

01:22:05.120 | It's the fact that even though we know a lot

01:22:06.700 | about the human body and the various hormones

01:22:08.500 | and neuromodulators like dopamine, serotonin, et cetera,

01:22:10.940 | that are made, this landscape of peptides

01:22:13.620 | is an enormous one, and it's one for which

01:22:15.940 | we are just now really starting to appreciate

01:22:18.660 | how many different peptides the human body and brain make.

01:22:22.120 | Again, I don't think it's an overestimate

01:22:24.100 | to say that there are probably hundreds of thousands

01:22:26.200 | of different peptides, each with multiple

01:22:28.000 | and sometimes even overlapping and synergistic effects.

01:22:30.840 | So, I do understand the excitement

01:22:33.780 | about peptide therapeutics.

01:22:35.280 | I think for a lot of people that want to improve

01:22:37.020 | their physical health and mental health,

01:22:38.820 | they want to recover from injuries more quickly.

01:22:41.680 | Maybe they're seeking particular aesthetic changes

01:22:43.700 | or mood changes, et cetera.

01:22:45.360 | I understand the gravitational pull

01:22:47.080 | and the excitement of peptides,

01:22:49.080 | but I have noticed that the discussion around peptides,

01:22:51.720 | because it's in contrast often to the discussion

01:22:55.000 | around hormone therapies like testosterone therapy

01:22:57.240 | and estrogen therapy, people, I think,

01:23:01.680 | inadvertently assume that peptides are all safe

01:23:04.760 | or innocuous or that they are potent enough

01:23:08.160 | to do certain things that we want,

01:23:09.840 | but that because they're not hormone therapies per se,

01:23:12.520 | that they are free of side effects and risk.

01:23:15.360 | And in addition to wanting to teach you

01:23:17.780 | about some of the biology of these peptides

01:23:19.600 | and how they work and what they're designed to do,

01:23:21.600 | as well as some of their potential therapeutic benefits

01:23:23.920 | under the right conditions,

01:23:24.960 | again, working with a really good board certified physician

01:23:27.880 | and making sure that the sourcing is really clean

01:23:30.240 | and that you're doing regular blood testing

01:23:32.540 | and you're monitoring for any potential tumor growth,

01:23:34.600 | et cetera, I also want to emphasize

01:23:36.800 | that these are very potent compounds.

01:23:38.920 | They have lots of different effects.

01:23:40.400 | And we are in the early stages

01:23:42.160 | of exploring peptide therapeutics.

01:23:44.200 | Again, I'm not here to tell you what to do

01:23:45.960 | or what not to do, but if you have it in mind

01:23:48.160 | that peptide therapeutics,

01:23:49.200 | because they aren't hormone therapies,

01:23:51.240 | are not without their potential risks, you would be wrong.

01:23:54.440 | All of that said, it's very exciting to see

01:23:56.560 | what's happening with peptide therapeutics.

01:23:58.240 | I'm excited about their potential

01:24:00.440 | for both the treatment of disease,

01:24:02.000 | as well as for augmentation of mental and physical health.

01:24:05.520 | And I think it's an exciting landscape

01:24:07.320 | that certainly motivated my desire to do this episode

01:24:10.080 | and get you familiar with them,

01:24:11.400 | or at least with some of them.

01:24:12.480 | And it's something that we're definitely going

01:24:13.940 | to be exploring more on this podcast,

01:24:15.960 | both with expert guests and in solo episodes going forward.

01:24:19.680 | If you're learning from and are enjoying this podcast,

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01:24:35.880 | and throughout today's episode.

01:24:37.280 | That's the best way to support this podcast.

01:24:39.920 | If you have questions for me or comments about the podcast,

01:24:42.440 | or guests or topics that you'd like me to cover

01:24:44.140 | on the Huberman Lab Podcast,

01:24:45.600 | please put those in the comment section on YouTube.

01:24:47.880 | I do read all the comments.

01:24:49.560 | Not so much on today's episode,

01:24:51.100 | but on many previous episodes of the Huberman Lab Podcast,

01:24:53.880 | we discuss supplements.

01:24:55.320 | While supplements aren't necessary for everybody,

01:24:57.340 | many people derive tremendous benefit from them

01:24:59.600 | for things like improving sleep,

01:25:01.020 | for hormone support, and for focus.

01:25:03.200 | The Huberman Lab Podcast

01:25:04.320 | has partnered with Momentus Supplements,

01:25:05.880 | and we've done that for several reasons.

01:25:07.640 | First, Momentus Supplements are of the very highest quality.

01:25:10.580 | Second, Momentus tends to focus

01:25:12.100 | on single ingredient formulations,

01:25:13.980 | which is essential in order to develop

01:25:16.180 | the most biologically effective

01:25:17.500 | and cost-effective supplement regimen for you.

01:25:20.100 | Third, Momentus ships internationally,

01:25:22.160 | which we realize is important

01:25:23.380 | because many of you reside outside of the United States.

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01:25:32.140 | so it's livemomentus.com/huberman.

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01:25:44.100 | And at all of those places,

01:25:45.500 | I discuss science and science-related tools,

01:25:47.500 | some of which overlaps with the content

01:25:49.180 | of the Huberman Lab Podcast,

01:25:50.380 | but much of which is distinct

01:25:51.540 | from the content of the Huberman Lab Podcast.

01:25:53.700 | Again, it's Huberman Lab on all social media platforms.

01:25:56.960 | If you haven't already subscribed

01:25:58.160 | to our Neural Network Newsletter,

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01:26:26.340 | Thank you once again for joining me for today's discussion

01:26:29.220 | about the science and application of peptide therapeutics.

01:26:32.540 | And last, but certainly not least,

01:26:34.800 | thank you for your interest in science.

01:26:36.700 | [MUSIC PLAYING]

01:26:40.060 | you

Benefits & Risks of Peptide Therapeutics for Physical & Mental Health

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