[Note: Dr. Gorski had a death in the family Saturday night and, as a result, won’t be posting anything this week. He will return to regular posting next week.]
So-called “peptides” are a fad that rivals some of the riskiest past health crazes I’ve seen, including unproven stem cells, but the peptide mania poses unique risks.
For context, more than 100 peptides have been FDA approved for legitimate purposes since the introduction of insulin in 1923, all the way up to and including GLP-1 drugs. These scientifically-proven peptide drugs are currently prescribed for conditions including diabetes, osteoporosis, chronic pain, and rare genetic disorders. But those peptides and uses are not what this post is about.
Instead, I’m covering the unproven and non-FDA-approved peptides that seem to be everywhere now. This fad also has become wrapped up in politics related to HHS Secretary RFK Jr, who apparently is a peptide enthusiast. There are notable parallels between marketing of unproven stem cells and peptides, including Kennedy’s interest in both.
The peptide craze took off in the US around 2020 when a constellation of physicians, wellness influencers, and firms like compounding pharmacies started making these unproven snippets of amino acids available to Americans. Many of those cashing in on the half-dozen or so most popular peptides like BPC-157, GHK-Cu, TB-500, and others (I’ll loosely call these “pop peptides”) claim without any solid evidence that these substances can do many good things in people ranging from increasing muscle to regenerating tissues to making you live longer.
Prescription not always required
As compounders and others started preparing pop peptides for customers, you’d think that a prescription would be required, but I’m not sure that always happened. I also wonder if some firms were producing peptides in bulk for dubious suppliers, who then sold them to influencers or directly to consumers. In the summer of 2022, a compounding industry newsletter rightly urged caution on pop peptides. It noted, “Wise prescribers will stay away from any entity that prepares or distributes peptide products for individual patients without a prescription. They’re not compounding pharmacies, and they’re likely violating state and/or federal law.”
Whatever the source, Americans either popped the peptides orally or got them injected. Some laypeople were even self-injecting. For a few years the FDA wasn’t carefully overseeing this space or maybe trying to play catch up, and these peptides floated in a regulatory gray area. The same kind of thing happened with unproven stem cells, where eventually more than one thousand stem cell clinics had spread around the country before the FDA did much of anything, such as seeking injunctions.
FDA action
Fortunately, in 2023, the agency put most of the pop peptides off limits to compounding by reclassifying them as Category 2, effectively barring compounding pharmacies from making them due to safety concerns, lack of data, or impurities. As a result, BPC-157, GHK-Cu (for injectable routes of administration), and most of the other pop peptides could no longer legally be compounded. This law firm webpage cautions potential suppliers on the legality of such peptide use now that they have been placed in Category 2. Note that the FDA seems to allow topical use of the peptide GHK-Cu, an application that is not considered Category 2. However, to be clear, no pop peptide has FDA approval for any supposed wellness application.
The Category 2 classification of most pop peptides was a positive public safety move by the FDA. To my knowledge, there hasn’t been even one medium-sized, well-controlled clinical trial of injection of BPC-157 or similar peptides in humans for a specific condition. Most of the studies on the pop peptides were done in rodents or in cell cultures in plastic dishes in the lab.
What does the research tell us?
I found only one vague listing on Clinicaltrials.gov for a phase 1 study of BPC-157 where the results were submitted but then cancelled before quality control took place. Yet somehow there are 207 articles on PubMed. They report a hodge-podge of animal and cell culture studies, along with opinion pieces sometimes touting the peptide. Other peptides like GHK have also been the subject of many animal and cell culture studies. Here too, the publication record contains little data on human use including especially by injection.
A review on BPC-157 published this past December rightly noted the lack of human data and the uncertainties arising from that. While this review also noted encouraging pre-clinical animal data on BPC-157, that doesn’t prove anything for humans and the authors cautioned about possible publication bias. I also wonder about potential conflicts of interest of authors of many of the publications that seem so upbeat about peptides. For instance, how many have no financial ties to BPC-157?
Backlash to peptide restrictions
The 2023 FDA action prompted a strong reaction. Some compounders, wellness influencers, and other companies profiting from peptides objected. There was at least one peptide-related lawsuit against the FDA, a case that was ultimately settled in a way that, to the best of my knowledge, did not open the door to resuming compounding.
Despite the grumpiness from those in the peptide world (there’s even a ‘save the peptides’ website), the FDA wasn’t somehow acting unreasonably on peptides. The US and world anti-doping agencies have also banned BPC-157. The US Anti-Doping Agency even has a BPC-157 doping webpage. If anything, overall the FDA had been too tolerant of unapproved peptide drugs.
It’s also important to consider the route of peptide use. While supposed wellness influencers largely promote peptide injection, there is also a vast array of oral supplements containing pop peptides. Although some synthetic peptides may be resistant to destruction in the GI tract, I suspect that many taken orally are quickly digested and then have no chance for meaningful activity in humans, if they even had any to begin with, which remains unclear. Even though many pop peptide formulations are often marketed as supplements, it’s unclear whether that allows them to escape drug classification.
Prohibition, gray markets, and risks
You might think the peptide problem would have eased since the FDA prohibited their compounding, but instead it appears to have worsened, and the scope of potentially dangerous peptide use in the US is astounding. Perhaps a million or more Americans have gotten non-FDA-approved peptide drugs at least once. There are peptide parties, peptide stacks (taking two or more peptides together), conferences and businesses that give free peptides as perks, and “peptide guys” who supply them for personal use.
Since American compounding pharmacies for now can no longer legally market these peptide drugs (although perhaps a few still do under the radar), where are people getting all these peptides lately? There has been a big shift to a gray market. Research-grade peptides are flooding the U.S., often coming from other countries, including Chinese suppliers. A recent New York Times piece on Chinese peptides in the US is a sobering read. Remarkably, users are often now instructed to DIY reconstitute the peptide powder with sterile water and then inject themselves. Not only does this risk infection, but also there’s often no medical provider around should something go wrong.
Of course, using research-grade pop peptides comes with all kinds of other risks. They can contain contaminants, including chemical residues related to their synthesis, and may come with incomplete peptides that might have even more unpredictable activities. The gray market vials may also contain the wrong peptide, an incorrect amount, no peptide, or who knows what.
The huge popularity of GLP-1 drugs, which are also peptides, may also be feeding into the pop peptide excitement. Perhaps it’s not surprising then that the overall peptide trend goes beyond BPC-157 and the other supposed wellness peptides to also include unproven and non-FDA-approved GLP-1-related peptides too.
Taken together, this is a major public health problem. Two women at a longevity meeting were hospitalized right after peptide infusions, but there are no details as to which peptides may have made them so ill. There was another recent report of necrotizing pancreatitis after peptide use. Such reports may just be the tip of the iceberg.
Since good clinical trial data are lacking, there is no way to know what any particular peptide injection might do to the body. There is also no solid information on dosage, potential interactions with other peptides or drugs, or longer-term risks. Given the lack of clinical trial data, it’s very possible that those who regularly take these peptides could have elevated risks of diseases that will only become apparent years down the road. I’m thinking of things like kidney or liver damage, immune issues, and elevated cancer risk.
Regulatory cop out coming?
Despite the risks and the fact that these are unapproved drugs, I’m hearing that an announcement could come as soon as within a month that the FDA will exercise what’s called enforcement discretion on the most popular group of these peptides. In other words, the agency would look the other way and allow compounding pharmacies to market pop peptides again, even though there’s been no clear change in the data on these substances.
Enforcement discretion in this case would be a political and regulatory shortcut (and I say a cop out) since changing actual relevant laws or regulations related to peptide compounding would be a lengthy, complex process.
Say what?
In a recent podcast, Tenille Davis, Chief Advocacy Officer for the Alliance for Pharmacy Compounding (which put out the 2022 newsletter I mentioned earlier), advocated for FDA enforcement discretion for certain peptide compounding (start listening around the 20-minute mark for the most relevant comments). Compounders argue that if there are no data proving these peptides are unsafe, they should be allowed to sell the peptides, even if there is also no evidence of efficacy in humans. That argument makes no sense, as all drugs—including peptides—must have strong data supporting safety and efficacy before marketing or the public is put at great risk.
Yet such arguments could win the day soon. HHS Secretary RFK Jr. seems quite interested in these peptides. GOP lawmakers have also asked him to weaken FDA oversight of peptides specifically through enforcement discretion. Note that one of the politicians who reached out to Kennedy co-owns a compounding pharmacy. Here, the arguments more generally are that consumers really want these peptides and, if compounding continues to be blocked, risky overseas peptide use poses ongoing dangers that justify allowing American compounders to be the suppliers. I don’t buy either of these rationales even if gray-market peptides do pose additional risks. In the frenzy over these peptides, we should keep reminding ourselves that these pop peptides are unproven and unapproved drugs.
The drumbeat for less FDA oversight here definitely has a right-to-try (RTT) feel to it. RTT is also often invoked for unproven stem cell drugs as well, which has led to a slew of state legislation legalizing use of non-FDA-approved stem cell drugs, with the latest being the so-called Stem Cell Freedom Act of Wyoming. Some of the “stem cells” covered by these laws are not even real stem cells. How long until we see federal or state laws legalizing pop peptides? Maybe a Peptide Freedom Act? To a great extent it will depend on whether the FDA ties its own hands behind its back on compounding of these peptides via enforcement discretion, which is what the compounders seem to be anticipating.
The role of influencers
What has driven this continuing peptide craze even after the compounding was blocked?
In large part wellness influencers have maintained the fad. One name that keeps coming up is an influencer named Gary Brecka, who is linked to Kennedy. It was on Brecka’s podcast that Kennedy disclosed getting unproven stem cells. The podcast also promotes pop peptide use and Brecka offers forms of BPC-157 and other peptides.
Many other influencers also engage in such promotion, either directly or indirectly, such as by enthusiastically stating they take the peptides. Eric Topol has a helpful post on the peptide craze that lists influencers and associated peptides. For example, remarkably, Topol indicates that Stanford professor and podcaster Andrew Huberman has in some way advocated for nine different unproven peptides. Joe Rogan promotes BPC-157 and influencer Dave Asprey is listed as advocating for “various peptides.”
Reply hazy, try again
It’s possible the FDA will take dual actions on peptides. It may crack down on gray market peptide import, while allowing American compounders to make and provide the products again. By the way, it’s doubtful that unproven peptide drug import into the US is remotely legal. That’s probably why the packages reportedly can be falsely labelled as though they are something else and “for research use.” What’s really in the little glass vials of white powder that show up at your house? There are now new firms sprouting up that will analyze the peptides you’ve gotten, including for purity, before you take them.
Admittedly, the US compounders seem to have made far better products, but the peptides are still unproven. Still, the compounders have major sway now. There was an entire session on compounding at Kennedy’s MAHA meeting last November. One of the panelists was Brigham Buhler of Ways2Well, which has marketed peptides. Asprey was also a panel moderator at the MAHA meeting.
Within the FDA, I had originally thought that its biologics branch CBER would oversee these pop peptides, but it turns out that the drug branch CDER is responsible for what are officially considered “peptides”, defined as chains of 40 amino acids or less. Anything longer than that is considered a protein instead, meaning a biological drug overseen by CBER.
CDER Director Tracy Beth Høeg seems likely to do whatever Kennedy and FDA Commissioner Marty Makary want on peptides. I don’t find it reassuring that Høeg previously had offered unproven stem cells. With an anticipated new Kennedy-friendly composition to the Pharmacy Compounding Advisory Committee (PCAC) related to its likely renewal as a committee by this April, PCAC may also facilitate softening of FDA oversight of pop peptide compounding.
A curious paradox
There’s a paradox with MAHA excitement about peptides. Many of the same folks who claim to be against food additives and proven vaccines will nonetheless inject themselves with risky peptides because some guru (who in many cases likely profits from the peptides) tells them it’ll do wonders
The FDA has a critical role in both properly overseeing pop peptides and educating the public about the risks of such products, but it seems the agency is soon more likely to make things worse than better on this front.