#387 – AMA #83: Peptides—evaluating the science, safety, and hype in a rapidly growing field

We discuss:

• Setting the framework for evaluating peptides, and explaining the goal of this discussion [3:15];
• What peptides are: basic definitions, biological roles, and therapeutic foundations [5:30];
• A framework for evaluating peptides: mechanism, evidence, safety, and regulatory context [10:00];
• Peptide case study—SS-31: mechanism of action, approved use in Barth syndrome, and other claimed effects [18:15];
• Does the mechanistic rationale for SS-31 translate into measurable benefits? [22:15];
• SS-31 continued: safety considerations, gray market risks, the balance of risk versus reward, and why it belongs in bucket #3 [26:00];
• Peptide case study—melanotan-II: claimed effects, mechanism of action, safety, and side effects [30:45];
• Melanotan-II continued: weighing the potential risks versus benefits and why it belongs in bucket #2 [36:30];
• Peptide case study—CJC-1295: growth hormone–stimulating mechanism, claimed effects, and limited human data [40:15];
• CJC-1295 continued: dosing uncertainty, risk-reward analysis, lack of long-term safety data, limited approved options, and why it belongs in bucket #2 [49:30];
• Peptide case study—BPC 157: uncertain origins, broad claims, and weak mechanistic evidence [57:45];
• BPC 157 continued: review of human evidence, lack of replication of animal data, safety considerations, risk-reward analysis, and why it belongs in bucket #1 [1:03:15];
• Other popular “gray market” peptides and why they mostly fail when under scrutiny [1:11:15];
• How the evidence on peptides compares to rapamycin, and why the lack of data is the biggest concern [1:20:00];
• Understanding peptide regulation: FDA approval, supplement oversight, and the risks of gray-market compounds [1:23:00];
• Inside the gray market: how peptides are sold, regulated, and why testing cannot guarantee safety [1:26:45];
• Limitations of oral peptides, and examples of peptides in bucket #4 [1:31:45];
• The future of peptides: real therapeutic potential versus hype in the wellness market [1:35:00]; and
• More.

Setting the framework for evaluating peptides, and explaining the goal of this discussion [3:15]

• Peptides are a topic we get asked about an insane amount
• The goal with this episode is not to promote or dismiss peptides overall, but just to give people a framework about how to think about them 

We will also explain 

• What are peptides
• Where is the science solid, weak, or non-existent? 
• How to evaluate the claims that people make? 
• With this, we’ll walk through a core set of questions that apply to any peptide, and we’ll apply it to a variety of popular
  • Do we know the mechanism of action?
  • What do we know about safety and dosing?
  • Is there any evidence that it can be helpful in humans? 
  • How to compare the risks and the potential benefits? 
  • Are there any other legitimate, approved solutions that are available? 
• At the end, we’ll zoom out and talk about the gray market space for peptides
  • Including how people should think about purity, sourcing, etc. 
• And then, we will truly end on the potential future of peptides
  • What new information would have to come out to really understand where these could be promising
• It’s a lot of different things to cover

Anything you want people to know before we get rolling? 

• The reason it has taken us so long to come out with this AMA is we wanted to do this justice

Peter adds, “We don’t do anything in moderation on this podcast, except for moderation. There’s a bar that just had to be cleared, I hope we’re about to clear it for you as a listener.”

What peptides are: basic definitions, biological roles, and therapeutic foundations [5:30]

Define what peptides are 

• It’s funny, Peter’s wife was asking him a peptide question at dinner over the weekend, and naturally, the 8-year-old and the 11-year old were like, “What are peptides?”

Peter explained to them, “Look, there’s nothing magical here. A peptide, it gets talked about in this health and wellness space like it’s something magical or new, but it’s not. A peptide is a short chain of amino acids.”

• He doesn’t think there’s a real clear definition of what constitutes a peptide versus a protein
  • Clearly, once you’re into the thousands of amino acids, you’re clearly talking about proteins
• Peter has read definitions that would suggest up to 60, up to 100 [amino acids], but the point is: it’s pretty small

A relatively short number of amino acids strung together forms a peptide 

• Sometimes it’s so short that it’s literally just a straight line of amino acids, and other times they form more complex structures—they form rings and things like that

Peptides are things that the body naturally produces (there are many examples)

• They serve all sorts of essential functions: they act as signaling molecules, neurotransmitters, they act to facilitate the transport of molecules, they sometimes can act as antioxidants
• Some of these peptides are going to sound really familiar
• Some of the most important things that people have heard of like endorphins, insulin, GLP-1 (these are all peptide hormones)

Some of these things can be produced synthetically 

• So we’re able to create peptide-based therapies that can mimic the endogenous or body-produced peptide 
• Again, Peter would say that the single most important of these would be insulin
  • Insulin was discovered roughly 100 years ago
  • It was clear that in a disease called type 1 diabetes, that people who lacked insulin because their beta cells were being attacked by their immune system were going to die, and if we couldn’t give them some form of insulin, that they were going to be in trouble
  • Initially that was done by taking insulin from dogs or pigs 
  • But ultimately, once insulin could be synthetically produced, you could create a therapy to save the life of somebody with type 1 diabetes
• More recently, people will be very familiar with the GLP-1s
  • We’re going to talk about that because in the GLP-1 world, we’re not typically giving people the exact same peptide, but we’ll come back to that

A lot of times when people are asking about peptide supplements, they’re not always referring to insulin or even GLP-1s 

What is the goal with peptides that you want to make sure we talk about today? 

• We’re going to talk about these a little differently
• We’re definitely not going to talk about insulin today
• We will talk a little bit about GLP-1, but from a sort of regulatory standpoint

In medical terms, a peptide broadly refers to an FDA-approved therapeutic molecule 

• Again, like insulin or GLP-1 drugs

Peter clarifies, “But in the more colloquial sense, the word peptide, as we are going to talk about it today, is more of the biohacking, pop science, bro science connotation that refers to various therapeutics that are touted for various benefits, often related to ‘longevity and beauty and tissue healing recovery performance,’ but they don’t have an FDA approval at all, or they’re being just used off label for any of these purposes.”

• So, when we’re going to talk about peptides, we’re going to be talking about things that are generally administered via injection that have become popular despite a lack of scientific or medical consensus on their efficacy 
• These are going to be things that are virtually all available through “gray market” means, and we’re going to talk about what that actually means, and why that’s necessary
  • By necessary, Peter means why that’s the means by which you would acquire these things
  • In which their sale isn’t technically illegal
  • But by marketing them for “research use only,”—they’re not approved for human use, but everybody understands that they are indeed being used by people

A framework for evaluating peptides: mechanism, evidence, safety, and regulatory context [10:00]

Given that a lot of these are gray market, not FDA-approved peptides, how do you recommend people start to think and evaluate the potential of whether they can be helpful or not?

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