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 public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is matina matina makes loose leaf and ready to drink yerbamate I often discuss ybba mate's benefits such as regulating blood sugar it's high antioxidant content the ways that it can improve digestion

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select 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 cancer I'd like to take a brief moment and thank one of our sponsors and that's ag1 ag1 is a vitamin mineral probiotic drink that also contains adaptogens I

started taking ag1 way back in 200 12 the reason I started taking it and the reason I still take it every day is that it ensures that I meet all of my quotas for vitamins and minerals and it ensures that I get enough Prebiotic and probiotic to support gut health now gut health is something that over the last 10 years we realized is not just important for the health of our gut but also for our immune system and for the production of neurotransmitters and neuromodulators things like dopamine and serotonin in other words gut health is

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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 resolved I'd like to take a quick break to acknowledge our sponsor element element is an electrolyte drink that has everything you need and nothing you don't that means zero sugar and the appropriate ratios of the electrolytes sodium magnesium

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the winter when the temperatures are cold and the environment tends to be dry if you'd like to try element you can go to drink element spelled l.com huberman to try a free sample pack again that's drink element.com huberman okay so there are definitely 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 going forward if you're learning from and are enjoying this podcast please subscribe to our YouTube channel that's a terrific 0 cost way to support us in addition please subscribe to the podcast on both Spotify and apple and on both Spotify and apple you can leave us up to a f-star

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