Benefits & Risks of Peptide Therapeutics for Physical & Mental Health

welcome to the huberman Lab podcast

where we discuss science and

science-based tools for everyday

[Music]

life I'm Andrew huberman and I'm a

professor of neurobiology and

Opthalmology at Stanford school of

medicine today we are discussing

peptides peptides are a topic that's

receiving a lot of attention these days

in part because of the excitement about

the so-called glp1 analoges or Agonist

glp1 stands for glucagon like peptides

these are drugs used to treat type 2

diabetes as well as drugs used to treat

obesity today we are not going to

discuss the glp1 analogues however we

are going to discuss some of the other

peptides that are receiving a lot of

attention these days including peptides

for tissue healing and repair as well as

peptides that impact longevity and

vitality now in principle any discussion

about peptides could be enormously vast

and that's because there are so many

different kinds of peptides and by the

way I will explain what a peptide is in

just a few moments but for instance

insulin which is involved in regulating

our blood sugar or blood glucose levels

is a peptide oxytocin which is sometimes

called the love hormone although I

wouldn't say that's the best description

of what oxytocin is it's a neuropeptide

hormone that is involved in everything

from parir bonding to socialization but

a bunch of other things as well those

are just two examples of peptides that

are familiar to most people at least by

name and that exist within the tens of

thousands if not hundreds of thousands

of different peptides that EX exist

within our brain and body today's

discussion is going to focus on peptides

that are increasingly being used for

therapeutic purposes and I want to point

out something very important about this

topic area first of all it is a topic

area for which there is a lot of

confusion the mere naming of the

peptides is confusing often times

they're referred to Simply by virtue of

acronyms and numbers like bpc 157 or

mk677 etc etc such that if you're not

really familiar with them it can be a

bit overwhelming and Confused

today I'm going to provide a very simple

organizational framework that will allow

you to understand what these different

therapeutic peptides are why certain

ones may be advantageous for certain

purposes of course also highlighting the

potential risks and in some case

outright dangers and I'll tell you how

they each work alone and in combination

toward achieving specific physical and

in some cases even mental health goals

I'd be remiss if I didn't say at the

outset here that a lot of what's

happening with applied therapeutic

peptide biology

falls into one of three categories there

are peptides that are being prescribed

by physicians so these are prescription

peptides for specific purposes these are

FDA approved there are other peptides

that reside in kind of a gray market

area you can purchase them online but

the safety and efficacy of those

peptides is a bit questionable in some

cases very questionable and I'll give

you some filters to determine uh which

category certain peptides fall into and

then of course there's the black market

peptides it is possible to buy peptides

online through any number of different

sources and of course I do not suggest

people purchase Black Market peptides

it's very clear that a lot of them are

contaminated with things that both in

the short term but especially in the

long term can be problematic so if

you're interested in understanding or

using therapeutic peptides today's

episode is for you before we begin I'd

like to emphasize that this podcast is

separate from my teaching and research

roles at Stanford it is however part of

my desire and effort to bring zero cost

to Consumer information about science

and science related tools to the general

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ju products so what is a peptide a

peptide is a small Protein that's made

up of little chains of amino acids now

the moment people hear protein they

usually think proteins that you eat or

perhaps they think about four calories

per gram of protein and that sort of

thing keep in mind that we have lots of

different kinds of proteins within our

body that have nothing to do with the

proteins that we eat now it is true that

many of the amino acids that comprise

peptides as well as other proteins in

the body come from the foods that we eat

because the amino acids again are the

building blocks of peptides and other

proteins the basic way that we Define a

peptide is that it tends to be a small

protein meaning chains of anywhere from

2 to 50 amino acids that's really the

strict definition of a peptide however

of often times peptides that are a

little bit bigger so maybe 75 or 100

amino acids in length will also be

considered a peptide now if you start

combining different peptides together

you get what's called poly peptides and

many of the proteins in the body are

poly peptides so just to get a mental

image of what a peptide is a peptide

basically looks like beads on a string

where there are two to 100 beads and

each of those beads represents a

different amino acid and the arrangement

of each amino acid relative to one

another that is their order along that

string determines what the peptide is

and what the peptide does the other

thing that's important to understand

about peptides is that some peptides are

hormones other peptides are merely

called peptides proteins others are

neuromodulators meaning they adjust the

activity of neurons and some peptides

multitask and do many things in fact I

think it's fair to say that most

peptides have what are called pleotropic

effects meaning they affect many

different aspects of cells and this is

very important to understand because

unlike a lot of our discussion on this

podcast about dopamine or about specific

hormones like testosterone or estrogen

when we talk about peptides especially

therapeutic peptides often times we're

talking about a single peptide that does

a bunch of different things depending on

the cell type the time of day or night

that that peptide is present and even

the different so-called Downstream

effects of the peptide what do I mean by

Downstream effects well when a peptide

binds to a receptor on a cell surface

okay and you can just think of that

process as a little parking spot on the

surface of a cell and the peptide if

it's available will bind to that

receptor and then set in motion a kind

of Bucket Brigade a sort of conveyor

belt of cellular processes for instance

activating one pathway for cellular

growth and another pathway for cell

migration for the cell to actually move

and maybe another Pathway to talk to

another cell to stimulate say the growth

of blood vessels in other words lots of

different or pleotropic effects this is

important because when we're talking

about peptide Therapeutics rarely if

ever are we talking about a very

targeted and very specific effect of

these peptides and this is important

both in terms of thinking about what

effects you're going to get of taking a

given peptide if you decide to do that

as well as potential side effects as

well as things like how to adjust dosage

and how long to take a peptide whether

or not to cycle the peptide Etc so I

just gave you a very simple description

of what a peptide is and the fact that

they have pleotropic meaning many

different effects both within cells and

across different cell types and of

course across different organ systems so

rarely if ever will you hear that a

peptide does one thing most often a

peptide does anywhere from four to maybe

even a thousand different things and

again we can go back to our basic

examples of peptides like insulin like

oxytocin and say for instance oxytocin

it's known to be involved in milk let

down during lactation it's also known to

be involved in pair bonding in both

males and females as well as pair

bonding between parent and child maybe

even parent and pet so the point is that

if you want a specific biological effect

maybe you want to repair a given injury

or you'd like to get more growth hormone

in order I don't know to get leaner or

to recover from exercise more quickly or

to feel more Vitality yes there are

peptides that can impact those Pathways

but always always always if you take

peptides especially theraputic peptides

designed to promote activity within a

given pathway for a specific purpose you

are going to activate other Pathways as

well there's simply no way to remove the

pleotropic feature of peptide

Therapeutics nowadays there's a lot of

interest and indeed growing interest in

peptide Therapeutics and there really

three different paths by which people

obtain these peptides the first is by

prescription from a board-certified

medical doctor so some peptides have

been approved for one use but they can

be prescribed also for off Lael use and

here we're talking about FDA approved

clinically tested peptides but many

cases they've been clinically tested for

one particular area of medicine so for

instance the peptide cellin which

promotes the release of growth hormone

has been FDA approved for the treatment

of short stature but it is often now

prescribed for other things as well

where a physician and their patient

agree that augmenting the growth hormone

pathway would be useful now regardless

of the specific use in mind it's

absolutely clear that the safest and

best situation if one is going to use

therapeutic peptides is to use

prescription therapeutic peptides where

the prescription comes from a board

certified physician and the reason for

that is severalfold first of all

sometimes these peptides come from

Pharma companies other times they are

made by a compounding pharmacy but in

both

situations they are cleaned of what's

called Lippy polysaccharide or LPS LPS

is something that can accumulate in the

manufacturing process of some of these

peptides and it's something that you

really want to remove from the peptide

before you ingest it or inject it most

peptides are injected either

subcutaneously or into the muscle

although some can be taken orally or

even a topical cream we'll talk a little

bit about different modes of delivery a

little bit later in any case getting the

LPS out and making sure that the peptide

is pure is very important the reason is

that LPS causes an immune response and

while a tiny amount of LPS might not

cause a massive immune response the

accumulation of many many LPs exposures

can start to become problematic and the

other sources of peptides which are gray

market and black market often times do

contain the same peptide that one would

get from a prescription from a board

certified physician but very often they

haven't cleaned out the Lippy

polysaccharide they haven't removed the

LPS and that can start to create

problems over time and of course in the

case of Black Market sources especially

often times the peptides are not what

they claim to be on the label or from a

particular source so that's especially

problematic so I want to be very clear

about my stance on this if you are going

to explore peptide Therapeutics I highly

highly recommend indeed I implore you to

do so with a board certified physician

and to acquire peptides through a

reliable source where the LPS has been

removed which typically means from a

pharmac company or from a compounding

pharmacy okay so let's talk about

specific peptides for specific purposes

today we're going to cover four general

areas in which peptide Therapeutics can

be useful the first is for rejuven ation

and repair of basically any tissue but

in particular muscle and connective

tissue so Sports type injuries but also

things like gut so for people that

suffer from IBS irritable bowel syndrome

or from colitis or from other gut issues

there is a potential use for therapeutic

peptides then we're going to discuss

therapeutic peptides for metabolism and

growth of frankly all tissues as soon as

people hear metabolism and growth

generally people think of fat loss and

muscle growth and indeed those fall

under this category but there are a

bunch of other tissues for which you may

want to improve metabolism and perhaps

growth as well so we'll get into that

then we'll discuss therapeutic peptides

specifically for longevity both staving

off tumor growth as well as potentially

and I want to highlight potentially

increasing lifespan although this is a

very experimental area at present and

then we'll talk about therapeutic

peptides for increasing Vitality both

mood and libido in both men and women

okay so let's discuss peptides for

Rejuvenation and repair of tissues now

it's pretty common to injure a given

tissue you know to uh you know strain a

tendon or tear a ligament or break a

bone or I don't know any number of

different things this is just kind of

part of life if you uh play sports or if

you exercise frequently sooner or later

people tend to get injured and when one

does there's you know a lot of different

things one can do there's a lot of

debate nowadays about whether or not you

should emphasize cold or whether or not

you should emphasize heat there seems to

be a growing

now the answer to this isn't entirely

clear and as I always say anytime you

want to answer a question about kind of

the why something evolved to be a

particular way you have to remember that

neither I nor anyone else was involved

in the design phase it's just is what it

is so we have to be careful about making

up just so stories about why something

is doing what it's doing or how it got

there so why would there be a peptide

within the gut that's involved in tissue

healing and repair well in order to

understand that it's important to

understand that the lining of your gut

all along it length involves a bunch of

different layers of cells that turn over

at a pretty frequent rate so unlike your

brain cells that for instance after

about age 25 you're not adding or

deleting many brain cells at least

provided there's no injury or nerve

degenerative disease you're not removing

a lot of those brain cells but you're

also not adding many brain cells there

are few areas of the brain like the

olfactory bulb and the dentate dryers of

the hippocampus where there is some

turnover but for the most part the

neurons you have at about age 25 are the

neurons that you're going to have for

the rest of your life your gut is very

different within the millu of the gut

you have a lot of turnover of cells and

the turnover of cells in the gut is in

many ways the same sort of turnover

process that's involved in wound healing

and repair like if you cut your skin

another tissue or organ in this case

that involves a lot of turnover of cells

because as you know if you cut your skin

at some point it will heal up you know

first there'll be a scab then that scab

will um give way as the tissue

underneath it mends and that mending of

the tissue is the addition of new skin

cells as well as other cell types so the

fact that there is a peptide in our gut

that can be involved in tissue turnover

and tissue turnover is equivalent to

tissue repair is not all that surprising

now it's important to understand that

anytime we're discussing tissue

Rejuvenation that is cellular turnover

or tissue repair so any kind of wound

healing a small wound or a big wound it

almost certainly is going to involve

angiogenesis which is the development of

new vascular Supply or blood supply now

of course vascular Supply arrives

by capillaries veins and arteries and

typically when we're talking about

angiogenesis in the context of tissue

Rejuvenation and repair we're talking

about the addition of new capillaries

and or blood vessels and that means the

addition of new what are called

endothelial cells which are the cells

that make up the walls of those blood

vessels so put simply if you want to

rejuvenate a tissue or you want to

repair a tissue you need additional

blood supply and one of the clear

effects of bpc-157 is to both encourage

cellular turnover as well as cellular

migration so new cells and cells moving

into a given area as well as new blood

supply through the promotion of this

process we call angiogenesis so you can

imagine for instance that maybe you U

injure your elbow and you do so in a way

that impacts a bunch of different

tissues maybe some of the nerve cells

the neurons there are severed okay or

crushed so that might lead to some pain

there but it might also lead to some

inability to move that joint or that

limb as well as you could previously

probably also some damage or some

crushing to some ligament tissue and

some tendon tissue maybe even to some

musculature a bunch of different tissues

are impacted and one of the things that

bpc157 has been shown to do in animal

studies and I really want to emphasize

animal studies because that's where the

vast vast vast majority of data on

bpc157 come from well it's been shown to

increase blood flow to a given area by

virtue of increased angiogenesis so

basically to promote the development of

new blood vessels to the entire injury

site and the way it does that is very

interesting bpc-157 somehow is able to

recognize injured blood vessels and

injured capillaries and then to promote

the activity of a given enzyme called

Enos or endothelial nitric oxide

synthese which then causes more blood

vasculature to form at the injury site

and around the injury site that in turn

allows for the delivery not just of

blood but for the stuff that's contained

within blood including growth factors

that then promote the further

Rejuvenation of different cell types in

the given area so the things that could

potentially lead to repair of muscle

repair of ligament repair of tendon Etc

and then bpc157 is known to further

encourage the growth of capillaries and

veins within the injury area so it both

calls in the development of new

vasculature and it promotes the growth

of that new vasculature bpc-157 is also

known from animal studies to encourage

fiberblast migration and growth within a

site of injury fiberblast are a key cell

type within an injury and they provide

some of the really firm strong substrate

for bridging injuries and that allow

different things like tendons and

ligaments to restore themselves from say

torn or partially torn to a complete

tendon or ligament now there's a very

long and kind of interesting history of

the use of gastric juices okay I know

the term uh might make a few people

queasy but gastric juices to promote

tissue healing and repair now there's a

whole history of focusing on gast juices

or at least the stomach environment for

keeping given tissues alive so that they

can be repaired later I know this sounds

a bit gruesome but one can find in the

historical medical literature instances

of people say severing off a finger or

even a hand uh or things of that sort

and then it being placed by a surgeon of

course or in some cases these were

Battlefield um situations into the gut

as a way to preserve that finger or hand

and keep it alive essentially and then

to graft it back on or to make an

attempt to graft it back on so that the

person could then use those fingers or

that hand again and while not always

successful it was clear or at least the

idea started to form that tissues that

were placed inside the milu of the gut

stood a better chance of being grafted

back on now you could think of a number

of different factors that could impact

the improved grafting of tissues placed

in the gut until the graft could take

place you know it could be uh the heat

of the environment it could be

uh the fact that the hand or finger is

not exposed to things out in the world

so less bacteria Etc nonetheless

Physicians were intrigued by the idea

that maybe something within the gut

itself and in particular within gastric

juices were beneficial for preserving

and maybe even rejuvenating tissues and

one particular peptide compound turned

out to be bpc body protection compound

which again is synthesized as bpc157 so

there's a real logic here but what we

haven't really addressed is if one has

an injury let's say the hand or um to

the arm or to the leg or to the ankle or

to the Achilles tendon how is it the

body protection compound that normally

would exist within the gut actually

access that injured tissue now this

Still Remains somewhat of a mystery it

is clear that bpc 157 can exit the gut

but how it gets traffic to particular

sites within the body that are injured

still isn't clear that said within the

community of people that use bpc157 for

therapeutic reasons for tissue

Rejuvenation and repair there's sort of

been an ongoing debate as to whether or

not you can take it

systemically that is to inject it or

even take it orally and that it will

find the sight of injury right it'll go

direct itself to the S side of injury or

whether or not it's more beneficial to

inject it directly to the site of injury

and here there's really no formal

science I want to be really clear when

we talk about bpc 157 we can look to a

pretty large literature of peer-reviewed

studies dating back to about 1993 is

when the first kind of rigorous study of

bpc 157 really began and there

animal literature I even would go so far

as to say quality studies of bpc157 and

its effects in animal models such as

rats and mice and such a dir of formal

rigorous exploration of bpc157 in humans

and at the same time a gosh let's just

call it what it is a really rich set of

anic data meaning that many many people

perhaps even most people who take bpc

157 by the way the typical route of

taking bpc 157 is either to inject it

subcutaneously or into the muscle and to

do that regardless of where the injury

is they'll do that in one particular

site so subcutaneously just a few inches

off the belly button or into um you know

into the shoulder or something of that

sort if they're doing it intramuscularly

or in some cases people will direct it

to the side of injury by injecting more

local like if you have an elbow injury

they'll put into the muscle right above

the elbow or subcutaneously right above

the elbow and we're now in a situation

where we don't know if we're dealing

with pure placebo effect or we are

dealing with real effects and so because

of the lack of the human clinical

studies we don't know whether or not

we're dealing with a situation of robust

Placebo effects I did an episode all

about Placebo effects and Placebo

effects are and can be oh so real they

really um can really trick you into

thinking that a given compound is doing

something when in fact it's not doing

anything different than would an

injection of saline of saltwater but in

this case there's just such an

overwhelming amount of what I call anic

data and there are so many people using

bpc157 now and are interested in

starting to use bpc 157 that I'd be

remiss if I didn't discuss it despite

this Gap in the human clinical

literature so what do we know from the

anic data the anic data seem to indicate

that the mode of delivery that is

whether or not systemic or local doesn't

seem to matter that much although some

people for whatever reason will purport

that local injections serve recovery of

the tissue more readily than systemic

injections now there are a couple things

to understand about bpc 157 besides the

fact that in animal studies it's been

shown to increase fiberblast migration

to a sight of injury as well as

endothelial cell and Vascular growth to

a sight of injury and the first thing is

that injury seems to be important there

does seem to be something that the

injury signals to bpc157 to create new

vasculature and fiber blast growth there

at the site of injury there's no

evidence from these animal studies at

least to my knowledge that bpc157

systemically increases vascular growth

although one could imagine that it might

right and for that reason I'll talk

about some cautionary notes about bpc

157 as it relates to tumor growth and

Cancers and diseases in particular of

the eye that involve overgrowth of

vasculature but before I do that I want

to talk a little bit about the safety of

bpc-157 one of the reasons why it's

being used so extensively is that it

does seem to have very high safety

profiles at least with respect to the

lethal dosing right in order to find out

the lethal dose of something as you can

imagine unfortunately the way these

studies are done is they give animals

more and more that is higher and higher

doses of a given compound find out at

what point about 50% of the population

of those animals starts to die and then

that's the so-called ld50 at least

that's one crude way of describing it

the

ld50 of bpc 157 is incredibly High okay

it is as high as two grams okay two

grams 2,000 milligrams that is per

kilogram of body weight now that does

not mean please hear me on this that

does not mean that any one should be

taking High dosages of bpc 157 the

typical therapeutic doses that are

prescribed are anywhere from 300 to 500

micrograms

subcutaneously maybe two or three times

per week and that is typically done for

a course of about eight weeks and then

people typically cycle off for anywhere

from 8 to 10 weeks now when I say

typically I mean typically because there

are individuals that take bpc 157

consistently they just take it every day

and they'll just take it indefinitely

without any break I think that is a bad

idea and I want to also state that I am

not suggesting anyone run out and take

bpc 157 today's episode is really about

giving you information so that you can

make the determination whether or not

you even want to take bpc 157 or another

peptide and of course to really

seriously consider the sourcing issue

that we talked about earlier now what

would be a reason to avoid taking bpc

157 well the first relates to something

that many people take bpc 157 for

because they believe it's good for them

and it's some cases potentially could be

which is that in addition to increasing

fiberblast migration and angiogenesis

blood vessel development within a sight

of injury bpc157 is known to have a

small but nonetheless meaningful impact

on upregulating growth hormone receptors

now this can be a good thing if you're

trying to upregulate growth hormone

receptors at a given injury site so that

growth hormone which comes from the

pituitary and we'll talk a bit about

more later then can have a heightened

level of action at that tisssue and

growth hormone is involved in tissue

turnover and repair this is evident from

childhood where kids heal from wounds

much faster than uh adults heal from

wounds there's other reasons why kids

heal from wounds more quickly than

adults that relate to things like stuff

secret from the thymus Etc we'll talk

about that as well but this idea of

increasing growth hormone receptors at

the site of injury or around the site of

injury by injecting bpc157 locally to

the injury or even taking it

systemically is one thing that many

people think of as advantageous and

that's why they want to take bpc 157

however for some people perhaps people

who have a tumor in a given area an

increase in growth hormone receptors in

and around the tumor could potentially

increase the growth of the tumor and

that's one of the major issues with

bpc157 that's not often discussed which

is that if you have a tumor and tumors

thrive on increased blood flow because

they like to consume growth factors and

increased blood flow means increased

growth factors and other things that can

not just sustain but actually grow the

tumor well then by taking bpc 157 you

may be either maintaining or

accelerating the growth of a tumor that

would otherwise be removed or stay small

in other words bpc157 is a potential

tumor growth risk so if you have

knowledge of a given cancer or you're

concerned about tumors at all I would

encourage you to be very cautious about

the use of bpc157 in fact one way that

bpc157 creates this increase in

angiogenesis this increase in

vasculature is through upregulation of

something called ve F vegf which is

vascular endothelial growth factor now

there is a common treatment for cancers

which is a vastin a vastin is a veg F

inhibitor it's a drug that's designed to

fight tumors to reduce tumor size and

does so by inhibiting vegf whereas bpc

157 is doing the exact opposite it is

increasing levels of vegf to increase

angiogenesis so by logical extension if

you're concerned about tumors or cancer

of any kind bpc 157 is probably not

something that you want to explore so if

bpc 157 carries these risks why are so

many people interested in taking it or

taking it I think in large part that's

due to the fact that um the anic data

about bpc 157 is just so strong people

report all sorts of things like you know

they recovered from their shoulder

injury much faster there are these kind

of outrageous claims about people

recovering from complete tissue trans

sections and um indeed there the animal

data are pretty impressive I went into

the data that looked at sciatic ner

nerve regrowth after injury Achilles

tendon regrowth after injury and some of

these studies in rats involved a

complete transsection not just a partial

tear but a complete cut of a given

ligament or tendon or nerve pathway and

indeed the data are pretty impressive

that when bpc157 is applied systemically

right so given you know at the level of

the gut somehow it's able to travel to

the side of injury recognize that

something needs to be done there in

particular angiogenesis and fiberblast

infiltration and it does seem that on

average that these tissues repair faster

than they do if bpc 157 is not provided

but again the tumor concerns and the

lack of human data are a real concern

that everyone should be made aware of I

do not think that bpc157 is not without

its quote unquote side effects I do

think that we are now in a state of

widespread experimental use of bpc157

even though it can be obtained clean

without LPS from compounding pharmacies

and by prescription there are a lot of

people taking bpc1 15 7 and I just want

to return to the point I made earlier

which is that you know bpc 157 is

typically taken in these dosages of

about 300 to 500 micrograms you know two

to three times per week maybe even five

days per week if you're going to go down

this path of taking bpc 157 I would

encourage you to take the minimal

effective dose to not simply do it every

day and certainly to not do it

continuously and of course to monitor

your other health metrics for anything

that could potentially resemble cancer

or tumor growth because obviously

stimulating angiogenesis for wound

repair sounds like a great thing

recovering and being able to do your

workouts or play your sport or um move

about more comfortably of course a

wonderfully attractive thing to do isn't

that what we all want but obviously not

with the trade-off of growing a tumor or

developing a cancer or accelerating a

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huberman okay so we're still talking

about peptides for tissue Rejuvenation

and repair and we spent quite a bit of

time on bpc157 because that's one

getting a lot of attention nowadays

there's another one that's getting

increasing attention that's worth

mentioning which is thin beta 4 and a

related peptide which is tb500 which is

basically a truncated or a shortened

version of the thymus and beta4 peptide

remember the peptide are these strings

of amino acids like beads on a string

and thymosin beta 4 is something that

the body produces naturally from this

thing called the thymus which is present

in children and then disappears as we

get older and it's well known again this

is correlative but it's well known that

children recover more quickly from

injuries and indeed the degree of tissue

regrowth and the repair of wounds with

minimal scarring is so much greater in

young children and in children than it

is in adults and this is what gave rise

to the idea that perhaps some of the

peptides that are secreted from the

thymus such as thymus and beta 4 could

be involved in tissue Rejuvenation and

repair and that's what led to the

laboratory synthesis of thymus and beta

4 the full length peptide made in a lab

not by the thymus and then adults take

it okay or tb500 which is this truncated

slightly shorten version of thymus and

beta 4 which acts similarly to thymus

and beta 4 but has a kind of different

mode of action lasts a little bit longer

Etc now again we're in a situation where

there are vast amounts of animal data

studies on micer rats typically that

show that thymus and beta 4 can increase

the rate Andor thoroughness of wound

healing and repair but again there are

more and more people now taking thymus

in beta 4 for the purposes of tissue

Rejuvenation and repair and Report

positive effects now when we say

positive effects we have to stand back

and say well um what's the control

experiment you know how would they know

how quickly they would heal without the

thymus and beta 4 and there simply no

way to address that question you know my

whole purpose in doing this episode is

to highlight how these different

molecules ought to work how they've been

shown to work in animal models and

therefore how they might be working in

humans but again in the absence of

clinical trials we still don't know if

and how they are working in humans

nonetheless a lot of people are now

starting to take especially tb500 it's

often taken in commin with bpc157 and at

the level of mechanism the difference

between bpc 157 and thymus and beta4 is

that thymus and beta 4 really promotes

the growth and infiltration of all sorts

of different cell types associated with

tissue Rejuvenation and especially wound

healing and repair it's been shown to

promote stem cell proliferation it's

been shown to increase the growth of the

so-called extracell Matrix the stuff

around the cells that keeps the area

around the cells kind of rigid so that

um the tissue or the organ has more

stability right you can't just have a

bunch of cells with um a bunch of empty

space around them where they can move

about you want to have some rigidity to

the whole thing so the idea is that

thymus in beta 4 is promoting the

aggregation of a bunch of things

associated with tissue healing I've

noticed out there that a lot of people

talk about tb500 that is thymus and beta

4 in the context of being growth

promoting as far as I know it isn't

growth promoting it doesn't impact the

growth hormone pathway or other Pathways

associate with tissue growth rather it's

involved in tissue repair so what I just

discussed are the two major players are

the two most often used peptides

nowadays for tissue Rejuvenation and

repair we've got bpc 157 which you can

just basically frame up in your mind as

promoting angiogenesis and wound repair

through a variety of mechanisms but

mainly the addition of new vasculature

to the wound site and then we've got

thymosin beta 4 which is sometimes

referred to as tb500 which is just a

shorter synthesized version of thymosin

beta 4 which is a molecule known to come

from the thymus in children whether or

not it's solely responsible I doubt it's

solely responsible in fact for the

better tissue healing and repair seen in

children as opposed to adults we don't

know and yet it does seem at least

anecdotally that people are taking tb500

again either alone or in combination

with bpc 157 and at least to their mind

are reporting more thorough or more

rapid tissue Rejuvenation and repair so

the next category of peptide effects

that I'd like to talk about are the

effects of certain peptides on

metabolism and growth and any discussion

about metab abolism and growth by

definition has to include a discussion

about growth hormon so basically where

we're headed is a discussion about

peptides that can increased amounts of

growth hormone that are released in our

brain and body to have specific effects

in particular increases in metabolism

and increases in either muscle growth

and in some cases repair of tissues as

well although mainly muscle growth and

fat loss for those of you that aren't

familiar with growth hormone growth

hormone is a hormone that we naturally

make it's secreted from a gland called

the pituitary gland the pituitary sits

near the roof of the mouth and it

extends out of the stock of the brain

such that it can release hormones into

the general bloodstream the pituitary is

connected to the brain however so it can

get input from a brain area called the

hypothalamus and within the hypothalamus

there are neurons that can send signals

to the pituitary telling it to either

release growth hormone or to suppress

the release of growth hormone now early

in life when we are infants children

teenagers and so on WE secrete tons of

growth hor hormone in particular during

the early hours of sleep each night we

also secrete growth hormone a little bit

throughout the day but it's really in

sleep in which we have the greatest

degree of growth hormone release this is

one reason why babies and kids and

teenagers sleep so much is there's a lot

of growth hormone release and we tend to

grow that is the tissues and limbs of

our body tend to grow during sleep now

it's been well documented that after

about age 30 which is typically when

people experience their full stature

their full height although sometimes

there's a little bit of uh wiggle room

around that age typically after 30 the

amount of growth hormone that's released

each night and throughout the day is

reduced by about 15% for every decade of

Life as a consequence all of the things

that growth hormone does like

encouraging higher metabolism fat loss

the growth of muscle tissue Etc is

dramatically reduced as we go from 30 to

40 to 50 and on and on it's also the

case that naturally relased growth

hormone tends to have positive postive

effects on our mood and overall feelings

of well-being so it's also tied to our

feelings of Vitality or having feelings

of energy to do things and that's

because growth hormone potently

increases ATP production which is

involved in Energy and Metabolism in our

cells and as a consequence our overall

feelings of energy to just do things

mental or physical now there's another

hormone called igf-1 or insulin growth

factor one which is produced by the

liver insulin growth factor 1 does many

things similar to growth hormone and it

actually is Rel in response to growth

hormone so basically the way this works

is that there's a signal that comes from

the hypothalamus called growth hormone

relasing hormone and then that signal

stimulates the anterior pituitary to

release growth hormone growth hormone

then is circulated throughout the blood

it also can access the brain itself and

it does different things in different

tissues but again increases ATP

production for energy it is going to

cause tissue repair in some cases it's

also going to encourage growth of

tissues not just muscles but other

tissues that's why it's involved in

helping us achieve our full height our

full stature when growth hormone reaches

the liver it stimulates the release of

igf-1 which in turn does a number of

things that are both synergistic and

different that is it works both

similarly to growth hormone and does

some things in parallel that are a

little bit different as well in

particular things related to regulation

of blood sugar metabolism Etc all things

associated with kind of youthfulness

Vitality and energy so it's impossible

for me to say that growth hormone and

igf-1 do just one thing each they do

lots of different things in lots of

different tissues but hopefully from the

description I just gave you could see

why some people might be interested in

augmenting or increasing levels of

growth hormone Now growth hormone has

been sequenced and synthesized so you

can buy a synthetic version of growth

hormone and indeed some people will take

prescription growth hormone they'll take

this by uh typically it's an injection

that's given subcutaneously at night and

they achieve growth of tissues including

muscle Etc keep in mind that growth

hormone is indiscriminate with respect

to which tissues it grows so if you

happen have an existing tumor on a given

body part or within a given body part it

will encourage growth of that tumor as

well that's one of the reasons some

people are cautious about taking growth

hormone another reason why many people

are cautious about taking growth hormone

is that it is subject to what's called

negative feedback if your blood levels

of growth hormone are too high by virtue

of injecting growth hormone well then

the pituitary can register that and the

Brain can register that and then there's

a negative feedback that shuts down

growth hormone as a consequence people

have developed peptide Therapeutics that

stimulate the release of growth hormone

and thereby the release of igf-1 but not

by directly stimulating the growth

hormone pathway typically what these

peptides are are these are peptides that

mimic the sorts of things that are

typically released from the hypothalamus

onto the pituitary and in that way

stimulate the release of growth hormone

and downstream igf-1 so what these

things are typically called are

secretagogues these are peptide

molecules that have been synthesized in

a laboratory that stimulate the release

of growth hormone and thereby stimulate

the production of igf-1 now there are

two general categories of peptides for

stimulating the release of growth

hormone the first category oftentimes

are referred to as the ghrh peptides for

growth hormone releasing hormone

peptides now that name has certain

problems that we'll get to in a moment

but let's just leave it there for the

time being the second category are

What's called the growth hormone

releasing peptides right before we said

growth hormone releas ing hormones

that's the first category second ones

are the growth hormone releasing

peptides you can already tell why this

is getting confusing here's what I'm

going to do rather than use that

nomenclature which is the typical

nomenclature that's used and I must say

for which there's a lot of Errors when I

look out there on various YouTube videos

and I look within even some of the

reviews that have been written people

get things confused as to whether or not

a given peptide that one would use as a

therapeutic falls into one or the other

category and you'll see in a minute it's

a really important distinction instead

what I'm going to call these are

category one peptides and Category 2

peptides okay in general category one

peptides are going to be the ones that

have been most thoroughly tested in

humans in some cases in fact in several

cases are FDA approved for certain

conditions and yes are prescribed for

other off label effects again this would

be under what I'm calling type one

growth hormone secreting peptides is

celin celin is a synthetic compound

designed to mimic naturally occurring

growth hormone releasing

hormone that is FDA approved for the

treatment of short stature so you can

get this by prescription sometimes it

comes from a compounding pharmacy other

times it comes directly from PHA for the

name brand in any case celin has been

shown to mimic what is normally released

from the hypothalamus and stimulates the

pituitary to release growth hormone and

it does indeed cause increases in

circulating growth hormone and increases

in

igf-1 by the way the typical dosages of

celin that are um taken are anywhere

from 200 to 400 micrograms typically

that's done at night before sleep for

the reasons that we talked about before

and typically people will take it

anywhere from three times per week or

five times per week there are some

disadvantages to taking it continuously

7 days per week for long periods of time

there's some desensitization that can

occur not much but some can occur so

taking in that way celin has been shown

to increase circulating levels of growth

hormone and igf-1 and the the reason why

a lot of people seek to take cellin is

because they like the effects it

produces they like the Vitality they

like the muscle growth they like The Fat

Loss um it also can increase the amount

of deep sleep that you get I'll just be

completely forthcoming I've taken cellan

on and off for the last couple of years

I typically will take it anywhere from

one to two nights per week and I stop

taking it almost completely I'll still

take it every once in a great while but

the reason I stopped taking it is that I

noticed that it made the sleep in the

early part of my night very very deep

very robust but then I would wake up

wide awake or I would sleep till morning

and then at least according to my eight

sleep sleep tracker or my whoop sleep

tracker I wasn't getting nearly as much

rapid eye movement sleep as I normally

would so at least in my case and again

this is anic data it seemed to sort of

replace rapid eye movement sleep with

more deep sleep and rapid eye movement

sleep is critical for all sorts of

things that deep sleep can't achieve and

vice versa so you really want both so

this is one reason why I've basically

stopped taking Calin I'll occasionally

take it every once in a while but in

general I just you know stop taking it

because uh whatever the positive effects

might have been if I had taken it more

consistently the effects in depleting

rapid eye movement sleep were just

something I didn't want and don't want

and by the way that effect on increasing

deep sleep that non-r sleep is something

that's pretty well documented the other

what I'm calling type one growth hormone

promoting peptide is tesamorelin this

goes by the brand name grifta and it's

an FDA approved drug for the reduction

of visceral adiposity in HIV patients so

we have subcutaneous fat and we have

visceral fat around our organs visceral

fat can be really problematic and for

some people who have HIV or and for

people who don't have HIV the deposits

of visceral fat can be problematic for

their health and tesamorelin again also

called AG gria has been shown to reduce

visceral adiposity it also seems to

produce some of the other same effects

that celin produces the differences

between the two relate to small

differences in the amino acid sequence

for one peptide versus the other

tesamorelin is a bit more long lasting

than celin and therefore is taken

typically about three times per week not

five times per week now the third most

commonly used peptide in this category

of what I'm calling type one growth

hormone secreting peptides is cjc-1295

gosh I wish there was a um an easier

name CJ

c1295 is basically a variant of a

different growth hormone secreting

peptide that was sized previously to

which they add what's called a DAC a

drug Affinity complex it's a it's a

sequence that makes it very longlasting

so cjc-1295 typically is only taken

twice per week or even once per week

because its effects on increasing growth

hormone in igf-1 last several days which

may sound great to you especially if

you're somebody that doesn't like um

taking injections because these things

uh in general have to be uh delivered by

injection but keep in mind that cjc-1295

has entered clinical trials there was a

death within one of the clinical trials

that was related to cardiovascular

dysfunction it's known to cause some

fluid retention and increased fluid

volume which may have been related to

that cardiovascular death we don't know

okay this is all kind of speculation but

I would say if you are somebody

considering using a growth hormone

secreting

peptide the type one category is perhaps

and I'll give my explanation for why I

believe this to be the case perhaps the

most advantageous category to explore

and as I mentioned before you've got the

options of cellan and tessarin both of

which are FDA approved and for which

there's both animal and human data CJC

1295 despite still being in clinical

trials does have this kind of stain of a

death within the clinical trial and to

my mind given that there are decent

Alternatives in serel and or tesamorelin

I don't know why anyone would

specifically select cjc-1295

until all these safety issues have been

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other synthetic growth hormone relasing

hormone peptides that are out there but

I think these three that we've covered

serel and testelin and cjc-1295 account

for the vast majority of those i' put

into category one the other category

which I'm going to call category two

you'll also hear a lot about and they

operate a little bit differently these

peptides encourage the release of growth

hormone but they do so either by

mimicking or stimulating the release of

another peptide called gin some of you

may be familiar with gin because gin is

a peptide that increases in

concentration when we are hungry so it

stimulates hunger and it also stimulates

anxiety somewhat so you may be wondering

why would anyone want want to increased

levels of growth hormone and gin and the

reason is that the Gin itself can impact

the growth hormone pathway pretty

potently so you can get really robust

increases in growth hormone but because

there are gin increases as well you get

big increases in hunger and anxiety in

some people and lesser in others now the

different names of the peptides in this

type two category are ones that you'll

hear kicked around a lot these days

things like ipom marelin okay so don't

get ipom marelin confused with

tesamorelin right tesamorelin is a type

one growth hormone relasing hormone pep

iin is in this Category 2 so it's

definitely going to increase gin which

is going to increase hunger it does have

certain advantages in particular that it

increases growth hormone release by two

mechanisms it increases it directly and

it tends to suppress something called

somatostatin somatostatin is a bit of a

break or an antagonist on growth hormone

release so with iper maralin you're

essentially removing the break on growth

hormone release allowing more growth

hormone to be released such that you get

a lot of growth hormone released it also

tends to really improve sleep but again

by increasing the amount of deep sleep

we don't know whether or not it does

that to at the expense of rap and eye

movement sleep so iprom marelin is the

most commonly discussed one in this type

two category the other one that you'll

hear about is called hexarelin hexarelin

is available by prescription and it is

the strongest stimulator of growth

hormone release which leads many people

to think okay I want hexarelin that's

the one that's going to give me the

biggest growth hormone pulse and indeed

the growth hormone Pulses from hexarelin

can be as great as two two or three

times more than with the other growth

hormone secreting peptides that we've

talked about however we know that

hexarelin can also dramatically increase

prolactin which can cause suppression in

libido it can cause fluid retention it

can cause a kind of feeling of malaise

especially a high levels and perhaps

most problematically hexarelin can

desensitize The receptors for growth

hormone releasing hormone such that your

system will no longer respond either to

the hexarelin or to any other peptide or

perhaps most importantly to any

endogenous that is naturally made grow

growth hormone excuse me releasing

hormone that you would make okay so

that's something to really consider if

you're going to explore hexarelin make

sure please that you're working with a

physician make sure that you're not

taking too much of it or for too long

and keep an eye on those prolactin

levels because those can be problematic

if they get too high and you know by my

read I can't see why anyone would use

high doses of hexarelin maybe low doses

of hexarelin if your doctor thinks

that's what's appropriate for you but

you'd really want to avoid that receptor

desensitization because you could

essentially turn off the system

permanently now there are a bunch of

other what I'm calling type 2 growth

hormone promoting peptides these include

ghrp2 ghrp 3 ghrp 6 again different

amino acid sequences all designed to

achieve the same thing which is more

growth hormone things like ghrp 3 can

potently increase growth hormone but are

known to also potently increase

prolactin and cortisol leading to more

than a doubling of circulating cortisol

ol which depending on how well regulated

it is across the time of day can be

problematic in other words you want

cortisol levels pretty high in the early

part of the day but you want them very

very low in the later part of the day

and at night and keep in mind that

almost always these growth hormone

peptides whether or not they're type one

or type two peptides are taken before

bed typically you know 20 to 30 minutes

before sleep always it's suggested that

they be taken at least an hour and a

half after eating any food and that you

don't eat for at least 30 minutes

afterwards because if you happen to have

elevated blood sugar or you've got food

in your gut they're not going to have as

potent an effect at increasing growth

hormone and igf-1 so again you want to

avoid uh food in the hour and a half

probably two hours before taking them

and certainly in the half hour or uh

longer after which is why most people

take them right before going to sleep

and add or augment that big growth

hormone pulse that occurs in the in the

early part of the night and then many

people have perhaps heard of what's

called

mk677 which is simply an oral version a

non-injectable but oral version of these

ghrps and it tends to have the same

issues that the other ghrps have which

are elevated cortisol and in some cases

elevated prolactin as well okay so if we

just kind to zoom out from all this we

can say that yes indeed there are

synthetic peptides that can potently

increase growth hormone in

igf-1 I explain the rationale for why

people would want that or perhaps to

explore that I'm certainly not

suggesting anyone um do this again I am

suggesting that if you do explore it you

work with a board certified

physician and that you get these

compounds from a quality compounding

pharmacy or by their name brand

prescription in type one we've got

cellin and Tess morelan both are FDA

approved for certain purposes they're

being used off label for increasing

growth hormone and igf-1 for the sorts

of things we're talking about

here they are taken anywhere from three

times per week to five times per week

keep in mind tessarin lasts a little bit

longer than cellan CJC 1295 is the third

in that category of type 1 growth

hormone secreting peptides but it may

again may we don't know have some safety

issues that still need to be resolved

making suelin and testelin at least to

my mind better options should you decide

to go down this path the type two growth

hormone releasing peptides include

things like hexarelin which are very

potent at increasing growth hormone but

can potentially increase other things as

well but of more concern is really that

it can cause receptor defenses ation

maybe even turn off the whole receptor

pathway that would not be good hyper

morelan again increases growth hormone

directly and allows more of it to be

released by suppressing its break its

natural break which is suat Statin and

then the ghrp 2 3 6 and

mk677 all of which can potently increase

growth hormone need to be considered in

light of the fact that they cause big

increases in cortisol and in some cases

can cause some receptor internalization

or desensitization as well although not

as potently as hexarelin so hopefully

that description clarifies some of what

you've heard out there um about these

different compounds and their different

names Etc it can be very confusing I did

take the liberty of designating a type

one and a type two category I did that

for sake of clarity because there are a

lot of different acronyms and numbers

Etc that can be really confusing to

people and I hope that that will be

useful in facilitating further

discussions about these compounds going

forward two additional brief but

important points many of the peptide

vendors that are out there and

Physicians that are working with

peptides will combine different growth

hormone promoting peptides so they'll

for instance have celin or testelin in

combination with hexarelin or they'll

use iprom marelin in combination with

CJC 1295 while I'm not opposed to that

approach you just want to make sure that

the dosing or I should say the relative

dosing of each peptide is such that you

know you're avoiding unnecessary

increases in prolactin and cortisol and

that you're not hitting a pathway

redundantly that's actually the logic of

combining different things these

different amino acid sequences these

different peptides that is are designed

to stimulate different modes of action

for the same peptide so the naturally

occurring peptide goes and does a bunch

of things those pleotropic effects and

these different peptides that are of

different amino acid sequences are

designed to you know reduce uh visceral

osity a bit more or promote deep sleep a

bit more or to promote muscle growth a

bit more so when people are combining

different things in cocktail it's not

necessarily a bad thing but you want to

make sure that you're working with

someone who's very familiar with

peptides you know really has been in the

peptide space for a long time and

understands how these things work alone

and in combination and there are some

excellent Physicians that are doing that

um and we plan to have at least one of

them on the Hub Lab podcast as a guest

in the not too distant future and you

can bet that this conversation will

facilitate your understanding of that

discussion the second point is that

there are of course risks to taking

anything but in particular to exploring

augmentation of the growth hormone

pathway when people take growth hormone

itself there are common risks such as

carpal tunnel syndrome um that has to do

in part with the fact that it can

potently increase cartilage growth there

can be active changes in the structure

of one's head and face and body there's

a so-called um uh lean but distended gut

so people that aren't carrying a lot of

uh subcutaneous fat but that the gut

becomes uh extended sometimes you can

get changes in the face like the um you

know kind of a a thickening of the of

the bone above the brow you'll see that

and sometimes people look quite

different after taking growth hormone

for a series of time than they did

before it can really change one's

stature and and shape uh to a

considerable degree it also can create a

kind of a uh kind of a a skin texture

that is a little bit unnatural or

unusual you sometimes can see this in

people that take a lot of growth hormone

in general when people take growth

hormone promoting peptides the changes

in body structure are not as dramatic as

when people take growth hormone itself

self but body shape changes and cosmetic

changes aside keep in mind that anytime

we augment growth hormone either by

taking growth hormone directly as a

synthetic compound or by taking a

peptide that increases the amount of

growth hormone that we release we are

increasing our tumor growth risk and our

cancer risk and that's because growth

hormone and igf-1 are somewhat

indiscriminant in terms of the tissues

that they promote the growth of so if

you have a tumor someplace and small

taking exogenous growth hormone or

increasing the amount of growth hormone

that you release by taking one of these

peptides that we discussed will increase

the size of that tumor it's very likely

and you can imagine that if you're

taking a peptide to increase growth

hormone and you're taking something like

bpc157 something that a lot of people

are starting to do

nowadays you could potentially increase

both the size and the vascularization of

a given tumor so just keep that in mind

just as there are anti-cancer drugs that

focus on the vegf pathway to try and

discourage

vascularization of tumors there are

drugs that discourage the release of

growth hormone to discourage the growth

of tumors so if you're listening to this

you might be thinking well why in the

world would anybody take this stuff well

people like the effects of having

elevated growth hormone they like the

effects of recovering from an injury

more quickly but there's always going to

be a trade-off between potential benefit

and potential risk the one thing that we

can say for these growth hormone

secretagogues serel and telin in

particular is that they are FDA appr

approved as compounds however they are

not approved for all the purposes that

people are taking them for such as

cosmetic effects Etc so I'm certainly

not being disparaging of people that

decide to make the choice to take these

compounds that's your right entirely but

I do think that you should be informed

about the potential risks and if you are

somebody who's considering taking any of

these compounds there are certain

considerations that you definitely

should pay attention to so for instance

how old are you if you're younger than

30 I don't know why you'd want to

augment growth hormone unless you and

your doctor decide that there's a

clinical need or some other urgent need

to do so uh because you're already

making a lot of growth hormone if you're

older than 30 and you're interested in

using these compounds to me it stands to

reason that of course you want to make

sure that you don't have any tumors or

cancers that you could potentially

exacerbate but in addition to that that

you really think about using the minimal

effective dose and that you use perhaps

even the mildest of these different

compounds in order to make sure that you

don't desensitize any of the receptor

Pathways and of course there is no

reason why anyone should use these

compounds unless they absolutely feel

need to and there's a potential benefit

there I personally as I mentioned before

tried cellin for a short while the

reductions in rapid eye movement sleep

were problematic enough for me that I

decided to just not take it and it's not

something that I've returned to except

every once in a great while I might do

it to augment deep sleep just a little

bit the next category of peptide effects

that we're going to discuss are peptides

involved in longevity and this is

actually going to be a pretty quick

discussion because really the main one

in this category besides thymus and beta

4 remember thymus and beta 4 we talked

about earlier this is a peptide that's

naturally released from the thymus and

the thymus is a structure that depletes

over time as children age so some people

will take thymos and beta 4 as kind of a

longevity agent hoping that it will

increase repair of tissues recovery from

exercise Etc but it's not really aimed

at longevity per se it's really aimed at

replacing something that's present in

Youth and then tends to dissipate as we

get older that is the thymus and related

peptides from the thymus but the big one

in the category of peptides to

potentially I want to highlight

potentially

improv longevity is epitalon epitalon is

also sometimes spelled and pronounced

epithin okay don't ask me why and as

with bpc 157 there are quite a few

animal studies exploring epithin and its

effects on various tissues as well as

the naturally occurring peptide that

it's meant to resemble epithin is a

peptide that's secreted from the pineal

gland the pineal gland is a gland that

most people associate with melatonin

release and that's because the cells

within the pineal called

pinealocytes secrete melatonin at night

it's what makes us feel sleepy and go to

sleep melatonin is suppressed by light

viewed by the eyes there's actually a

pathway that goes from the eyes into the

brain there a couple of stages they go

up through the cervical ganglion from

the brain stem and up to the pineal and

suppress melatonin release now the

pineal makes other things besides

melatonin it also makes a peptide called

epithalamion

from the pineal especially early in life

and that's associated with various

anti-inflammatory effects on other cells

and tissues in the body and it does

appear to be able to adjust tiir length

which is a feature of cells that's

thought to be associated with the

longevity of cells or how long they live

keep in mind that the relationship

between tiir and Longevity is a

controversial one people were very

excited about this some years back then

people batted down that idea showing

that kilometer length was not associated

with longevity especially in hum and now

it's sort of a back and forth within the

field keep in mind that epitalon again

also sometimes written and pronounced

epithin is designed to mimic this

naturally occurring peptide

epithalamic clature can get a little bit

confusing and what you'll find is that

epitalon is available as a synthetic

compound it can be obtained in clean

form from compounding pharmacies and a

good number of people will use it as a

longevity agent based largely on animal

data that it can suppress tumor growth

it can increase tiir length and to some

extent that it can recalibrate the

Circadian rhythm changes and the

disruptions in the patterns of melatonin

that occur as animals and perhaps as

humans age this is an important point

the pineal gland despite being very very

small about the size of a PE and sitting

kind of in the mid area of the brain for

you afficionados it sits you know kind

of like right on the roof of the Dian

sephylon

and what it does is it it will release

melatonin each night in

darkness it can release epithalamion and

at those times it can go and have these

Myriad effects on restoring the brain

and body during sleep there are other

things that occur during sleep that are

essential but those are key components

of the restorative features of sleep now

we know that as we age the amount of

melatonin that we release is decreased

such that if you look in babies and

teens Etc melatonin levels are very very

high compared to people of middle age

and of elderly age likewise epithalamion

levels decrease with time and as a

consequence markers of tissue

inflammation also increase as we age

because you're sort of removing this

anti-inflammatory compound that's

released each night now there are a

bunch of theories as to why the pineal

regresses with age there's some kind of

wild ones about fluoride and a depletion

of the of the pineal I'll do a whole

episode on the pineal at some point and

we'll explore that some of them are very

Niche some of them are frankly

completely false and others have some

Merit and are starting to um gain some

data within the standard scientific

Community the overall point here about

peptides for longevity can be summarized

very easily the logic is just as we have

a thymus early in life the thymus

secretes certain things and those things

seem to accelerate robust tissue healing

early in life and as the thymus

disappears tissue healing gets less

robust that's the logic for taking

things like thymus and beta 4

tb500 so too we have a

we know about the animal studies what we

know about the naturally occurring

compounds that these peptides are

designed to mimic and yet there are

still no clinical trials that point

directly to taking x amount of epitalon

several times per week as a way to

extend life the fourth and final

category of peptide effects that we're

going to talk about are effects on

Vitality both mood and libido and really

the main players within this category of

peptides are the so-called melanocyte

stimulating hormon related peptides okay

just to give you a little bit of

background remember the pituitary the

pituitary gland that stalk that extends

out of the brain and can release growth

hormone from the anterior pituitary well

it's got a middle segment or a medial

segment and there's a hormone that's

released from there called mocy

stimulating hormone melany stimulating

hormone has the effect of stimulating

pigmentation of the skin by activating

what are called melanocytes that exist

within the skin so the peptides

melanotan 1 melanotan 2 melanotan 3

Milan 4 Milan 5 because there are five

of them are different peptides that is

peptides with different amino acid

sequences all of which mimic naturally

occurring melany stimulating hormone but

that act preferentially on one set of

melany stimulating hormone receptors or

another in order to get different

effects so let's back up a little bit

and talk about the melanocortin system

right the melanocortin system is a

system whereby viewing light or getting

light on the skin typically Ultra violet

light of the ultraviolet B type okay

there's two different types of

ultraviolet light but basically sunlight

is what the system evolved to respond to

shown to the eyes and or to the skin

stimulates the melanocortin system it

goes from the eyes to the hypothalamus

from the hypothalamus to the pituitary

and then the melany stimulating hormone

is then released into the bloodstream

can travel to the melanoides and cause

pigmentation of the skin this is what is

responsible for SC there's also a

pathway whereby the light stimulates the

melany stimulating hormone system and in

parallel stimulates the release of

dopamine now for any of you that have

lived in a part of the world in which

it's very very dark with very short days

in the winter and longer days and a lot

of sunlight during the summer you're

probably familiar with the fact that

when the sun comes out people start

feeling better they have more energy

they're more motivated a number of

different systems related to mood and

libido tend to increase this is the

consequence of sunlight activating the

melano cortico system and by the way

this system is very active in other

animals as well animals that are white

or tend to be of pale color during the

winter then as spring arrives the

sunlight stimulates this very same

system and leads to darkening of the

pellage so their hair goes from white or

gray to Brown or even dark black or some

combination of those and in combination

dopamine is increased libido is

increased and the animals start breeding

in the spring and summer months okay so

this is a a well-conserved system across

species and it exists to some extent in

us as well so there are essentially five

different synthetic peptides called

melanotan 1 2 3 4 and five Each of which

is designed to mimic melany simulating

hormone but Each of which activates

different receptors to different degrees

and some can cross the blood brain

barrier and some can't and as a

consequence some impact mood and libido

and others don't the simple way to look

at this is that melanotan one does not

cross the bloodb brain barrier

it does however stimulate the

melanocytes of the skin so it leads to

tanning or darkening of the

skin melanotan 2 3 4 and five also lead

to darkening the skin by way of

activating melanocytes in the skin but

because they can cross the blood brain

barrier they cause effects that are at

the level of psychology really and at

the level of appetite and things of that

sort in general the pattern is to

increase mood in libido and to decrease

appetite things that are associated with

the transition from Winter to spring and

summer months in humans and in other

animals now one of the things about the

uh peptide literature is that it loves

acronyms and numbers and so there's a

peptide

pt41 that falls into this category of

activating the melanocortin system and

pt-141 is also known as the prescription

drug VII pt41 or VII is FDA approved for

the treatment of premenopause fusal

hypoactive sexual desire so this is FDA

approved for the treatment of women that

have suppressed libido however men also

will take VII um for hypoactive uh

sexual desire um this is obviously

prescribed off label um by physicians

but keep in mind as with the other

peptides in this pathway VII will

stimulate pigmentation so whether or not

you consider that a side effect or a

benefit depends on I guess your Baseline

level of pigmentation and how much level

of pigmentation you actually want now

there are some side effects associated

with these compounds and one of the more

common ones is nausea and that's because

there are melanite simulating um hormone

receptors all throughout the gut they

can also cause flushing of the skin and

they can cause blood pressure to

increase also folks with melanoma should

be very cautious about using any of the

peptides that stimulate melanocytes

because that could potentially

exacerbate melanoma the next peptide in

this category of peptides for Vitality

in libido is kisspeptin kisspeptin is a

peptide that wasn't discovered that long

ago actually you can recall when the

first papers about kisspeptin came out

and basically kisspeptin is a peptide

that is naturally made within the brain

and it's Upstream of some of the

hypothalamic signals that activate the

pituitary for sake of hormone production

and reproduction so I'll just walk you

through this pathway it's actually quite

simple you've got the pituitary you're

now familiar with the pituitary and the

pituitary releases two different hormon

hormones in both males and females it

releases lutenizing hormone and it

releases follicle stimulating hormone if

you watched the episodes that we did

about testosterone and estrogen if you

watch the episode that I did on male and

female fertility if you watch the

episode that I did with Dr Michael

Eisenberg from Stanford or Dr Natalie

Crawford who's an OBGYN uh specializing

infertility we talked a lot about LH and

FSH basically FSH as the name suggests

stimulates the growth of the follicle

the egg in the female and it stimulat

Ates sperm production in males

lutenizing hormone stimulates

testosterone production from the gonad

in males and it also stimulates estrogen

production and to some extent

testosterone production in females as

well so we need LH and FSH to stimulate

the gonads the ovary or the testes the

hormone that stimulates LH and FSH

release is called GnRH or gatot tropin

releasing hormone and it comes from the

hypothalamus so G&R is a signal that

promotes LH and FSH release now that

raises the question what turns on GnRH

and the signal that turns on G&R is

kisspeptin kisspeptin in other words is

further Upstream from G&R and lsh and

FSH it's a Cascade it goes kisspeptin

GnRH LH FSH testosterone estrogen okay

that's the pathway now it's very clear

that kisspeptin is involved in the

activation of puberty the transition

from prepubertal to postpubertal stages

of life it's also involved in any of the

sort of Downstream effects of having

elevated LH and FSH including elevated

Vitality which includes both energy and

in some cases libido so there's

naturally occurring kisspeptin and

there's now synthetically generated

kisspeptin designed to mimic naturally

occurring kisspeptin and it's actually

prescribed for what's called

hypothalamic amena hypothalamic amena is

the loss or the absence of periods of

cycles that are the consequence of

deficits within the hypothalamus itself

so not something within the ovary or a

lack of the pituitary to make LH or FSH

but a deficit of the hypothalamus to

promote LH and FSH and the downstream

hormones testosterone and estrogen

incidentally there are also kisspeptin

antagonists okay drugs that are designed

to suppress kisspeptin and those are

used to treat some of the symptoms of

menopause including night sweats and

some of the what are called vasomotor

symptoms so peptin is obviously a key

player in this whole pathway of steroid

hormone release the steroid hormones

being testosterone and estrogen there

are other steroid hormones as well of

course now there are folks within the

landscape of peptide Therapeutics folks

meaning Physicians and other

practitioners who said ah well here's a

a peptide that is known to promote all

these hormone Pathways that are

associated with Vitality libido Etc and

so there are people who take kisspeptin

peptides as a way to stimulate these

Pathways and they're doing so for the

specific purpose of increasing ing

Vitality as it relates to libido and

mood and to get the downstream increases

on testosterone and estrogen and of

course some people are taking kisspeptin

peptides to treat hypothalamic

amenorrhea and as I mentioned some

people are taking kisspeptin antagonist

they're trying to block the kisspeptin

pathway in order to reduce some of the

vasomotor and other symptoms of

menopause I will say despite the fact

that the ceptin pathway is well known

and despite the fact that the ceptin

peptide is designed to mimic a naturally

occurring peptide that has a pretty

constrained set of function

in the hypothalamic pituitary system and

their Downstream effects on the

gonads the use of Kiss peptin to

increase Vitality in libido is a bit of

a um let's just say it's it's a little

bit of a wild card we don't yet know all

the effects of kiss peptin again it was

fairly recently discovered we have it in

mind that it's involved in these

Pathways but I should say every time we

look at a given peptide whether or not

it's gin or hypocrite neurexin or it's

glp1 what we find is that again are

these pleotropic effects there is rarely

if ever one specific effect and it's not

just a concern about side effects that

we want to take these pleotropic effects

into consideration it's the fact that

even though we know a lot about the

human body and the various hormones and

neuromodulators like dopamine serotonin

Etc that are made this landscape of

peptides is an enormous one and it's one

for which we are just now really

starting to appreciate how many

different peptides the human body and

brain make again I don't think it's an

overestimate to say that they probably

hundreds of thousands of different

peptides each with multiple and

sometimes even overlapping and

synergistic effects so I do understand

the excitement about peptide

Therapeutics I think for a lot of people

that want to improve their physical

health and mental health they want to

recover from injuries more quickly maybe

they're seeking particular aesthetic

changes or mood changes Etc I understand

the gravitational pull and the

excitement of peptides but I have

noticed that the discussion around

peptides because it's in contrast often

to the disc discussion around hormone

therapies like testosterone therapy and

estrogen

therapy people I think inadvertently

assume that peptides are all safe or

innocuous or that they are potent enough

to do certain things that we want but

that because they're not hormone

therapies per se that they are free of

side effects and risk and in addition to

wanting to teach you about some of the

biology of these peptides and how they

work and what they're designed to do as

well as some of their potential

therapeutic benefits under the right

condition again working with a really

good board certified physician and

making sure that the sourcing is really

clean and that you're doing regular

blood testing and you're monitoring for

any potential tumor growth Etc I also

want to emphasize that these are very

potent compounds they have lots of

different effects and we are in the

early stages of exploring peptide

Therapeutics again I'm not here to tell

you what to do or what not to do but if

you have it in mind that peptide

Therapeutics because they aren't hormone

therapies are not without their

potential risks you would be wrong all

that said it's very exciting to see

what's happening with peptide

Therapeutics I'm excited about their

potential for both the treatment of

disease as well as for augmentation of

mental and physical health and I think

it's an exciting landscape that

certainly motivated my desire to do this

episode and get you familiar with them

or at least with some of them and it's

something that we're definitely going to

be exploring more on this podcast both

with expert guests and in Solo episodes

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