10 questions to ask your doctor about peptides

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Bigger muscles. Speedier injury healing. A longer life. Whatever the health or fitness concern, there's probably a peptide purported to address it. Indeed, the use of these injectable substances, many of which are not approved by the U.S. Food and Drug Administration (FDA), has fostered an estimated $2.2 billion underground market. In a recent survey, nearly half of doctors said they had a patient who admitted to using such peptides.

Earlier this year, the U.S. Department of Health and Human Services announced it was initiating a review process to consider removing a ban on the use of several of the most popular peptides. Later this month, the FDA's Pharmacy Compounding Advisory Committee (PCAC) is scheduled to meet to discuss adding these peptides to the list of substances that compounding pharmacies can include, thus legitimizing their use.

No matter the outcome, here's what you need to know about peptides, their functions in the body, and possible concerns.

1. What are peptides, and what do they do in the body?

Peptides are short chains of amino acids, the building blocks of proteins, says primary care and sports medicine specialist Anthony Tam, MD, chair of Family Medicine for Henry Ford Health in Jackson, Michigan. "They basically act as chemical messengers, delivering instructions from one cell to another," he explains.

These naturally occurring substances are responsible for a variety of different processes in the body, including telling cells when to grow, repairing tissue, releasing hormones, and fighting infection.

1. How are peptides currently used in medicine?

Synthesized peptides have been used in medicine as pharmaceuticals for decades, says endocrinologist Rekha Kumar, MD, associate professor of clinical medicine at Weill Cornell Medicine in New York City. For instance, "glucagonlike peptide 1 [GLP-1] receptor agonist drugs, such as Ozempic and Wegovy, are peptides, as are [the hormones] insulin, vasopressin, oxytocin, and human growth hormone. So, particularly in endocrinology, some of the oldest medicines are peptides."

Some peptides approved for a specific condition are being studied for other purposes, says Kumar. The FDA recently approved one of these, elamipretide, for the treatment of a rare genetic mitochondrial disorder. It's now being investigated for potential longevity benefits and as a treatment for age-related macular degeneration.

1. When people hear the word "peptides," they may think of those that wellness influencers are peddling through social media. What's different about these peptides?

Those peptides being marketed for longevity or performance have not been rigorously studied in human trials or approved by the FDA, says Kumar. They're legal to use only in experimental settings but are increasingly available online or from wellness clinics and other unregulated entities.

"There's a black market production, primarily in China, that sends large amounts of these peptides to the United States with the label 'For research only,'" says Pinchas Cohen, MD, dean and distinguished professor of gerontology, medicine, and biological sciences at the USC Leonard Davis School of Gerontology, who has discovered several investigational peptides. "Then, unscrupulous people take them and illegally compound them and sell them to questionable longevity clinics and gyms. It's now a multibillion-dollar industry."

Prominent examples of this market are the popular peptides known as BPC-157 and TB-500 - "peptides heavily advertised to help with tissue regeneration in the fitness space," Tam says. Such peptides are banned in professional sports.

1. What are other purported benefits of these peptides, and how are they being used?

It depends on the molecule, but different peptides claim to aid recovery, build muscle, enhance cognition, increase longevity, and even promote a deeper tan, among other possible perks. For instance, BPC-157 is touted for healing many types of injuries - from [those of the] tendons and muscles to the gut and brain, says Kumar.

"It's a repair and recovery peptide and is probably being used in some orthopedic practices, where it's injected into injuries and joints that have failed to recover from complex injuries or surgeries," she says. "In the longevity community it's being injected systematically for this broader concept of repair and healing."

Proponents believe that a peptide called GHK-Cu regenerates collagen and improves wound healing. And one called KPV is said to quell inflammation.

It's popular, in addition to injecting single peptides, to "stack" them - to use more than one at the same time, says Tam. The so-called Wolverine stack, for example, consists of both BPC-157 and TP-500.

"People will utilize these two injections together to help speed tissue repair or injury recovery," he adds.

Like the peptides themselves, however, the combinations of agents have not been well studied.

1. What research is there to support the health and fitness claims?

There's been very little human data to show a benefit from unapproved peptides, says Daniel M. Cushman, MD, professor of physical medicine and rehabilitation at the University of Utah Health. His own recent review of BPC-157 research found only three pilot studies for the peptide.

One study found positive effects on knee pain in 14 out of 16 patients. Another saw improvement in 12 patients with interstitial cystitis, a painful bladder condition. And the third, involving two healthy people, simply showed that BPC-157 was well tolerated, with no adverse effects.

Another review of studies involving BPC-157, as well as TB-500, GHK-Cu, and several other peptides, similarly found a lack of evidence to support clinical use of the substances.

Still, startling regenerative effects have been seen in animal studies of BPC-157, in particular; the peptide has been shown to promote the healing of tendons, ligaments, muscles, nerves, bones, teeth, corneas, and the endothelium, the lining of blood vessels. It was also found to aid recovery from brain injury.

Animal studies of TB-4 and its derivative TB-500 show that these peptides promote tissue repair and angiogenesis, the process by which new blood vessels are formed. Data on GHK-Cu suggest it has wound-healing and anti-inflammatory effects, according to the one study that reviewed several peptides.

"While peptide therapy may possess significant therapeutic and regenerative potential, it is critical that orthopedic and sports medicine providers understand the current lack of evidence to support the clinical use of these peptides," the authors concluded. "Importantly, information regarding the indications, dosing, frequency, and duration of treatment remains unknown. Despite the popularity of these peptides in mainstream media and among patients, significant research regarding the safety and efficacy of these therapeutic methods is required before definitive recommendations can be made to patients."

1. So, are more studies of these peptides in the works?

Not necessarily.

For example, "if you look on Clinicaltrials.gov, there are only two studies that even mention BPC-157," says Cushman. "There are a lot of factors that make it very hard to do a good study on these peptides."

For one, such research is costly, and the wide availability of unproven peptides makes them less attractive to pursue from a financial standpoint, he says.

"If you're going to study [them] properly, you're going to do a Phase 1 trial, a Phase 2 trial, a Phase 3 trial, and so on, and that's going to take a lot of money," Cushman says. "No pharmaceutical companies are going to sign up for that, because even if they make it all the way to approval, why would anyone buy it from them if they can already get it from China?"

1. What are the side effects of peptides? Are they safe?

Most peptides are injected, and irritation at the injection site is a common side effect. Other reported side effects include GI upset - nausea and vomiting - and headache.

Although short-term use of unapproved peptides appears to be mostly safe, "the larger concern lies with downstream side effects that we just don't know about," says Cushman.

For instance, one known effect of BPC-157, KPV, GHK-Cu, and other peptides is angiogenesis. Angiogenesis is essential for wound healing but can support the growth of tumors when cancer is present. That has led to the fear that these agents might promote malignancies.

"What if harm is being done?" says Cushman. "What are we going to say in 20 years when everyone is getting cancer from it? I need to know what we're giving patients rather than hoping that it's good and being on the cutting edge."

He and others are also concerned about the source of products.

"If people are getting them from research-grade pharmacies, that's the best possibility, because at least they're injecting what the pharmacy says they're injecting," says Cushman. "If you get it from other countries, it could be [a peptide], but it could just be saline or something bad. We don't know."

1. What's happening on the federal level with respect to peptides?

Under current regulations a number of widely used unapproved peptides are banned for use by compounding pharmacies in the United States. But later this month, U.S. Health and Human Services Secretary Robert F. Kennedy Jr. is convening a meeting of PCAC to consider changing the classification of seven popular peptides, thus allowing them to be compounded and sold by prescription. These include BPC-157, TB-500, KPV, MOTs-C, Emideltide, Semax, and Epitalon.

This action could bring some oversight to the unregulated industry.

"They'll review the available data, which involves some evidence of safety, to decide whether they should allow this new path," Cohen says. "It does not require proof of efficacy in large trials the way we typically expect from drugs, but it facilitates prescribing, and that changes things a lot, because there won't be a black market anymore. The compounding is going to happen in legitimate pharmacies, and [the peptides] will require a physician's prescription."

1. What is the larger promise of peptides?

Discovering and developing new peptides is a rapidly developing area of science, particularly peptides derived from the mysterious part of the human genome referred to as junk DNA.

"There are theoretically hundreds of thousands of these peptides," Cohen says. "We want to identify really useful peptides that can be leveraged and advanced as treatment for human diseases for which there is no solution at the moment."

One potential prospect is MOTs-C, which Cohen discovered and has studied in Phase 1A and Phase 1B trials. He stopped his research, though, when his biotech firm foundered.

"It's a muscle-sparing weight-loss drug," he says of MOTs-C. "It's much less potent than GLP-1s, but the muscle-sparing effect is important," as one-third of the weight lost on GLP-1s is muscle mass. The use of MOTs-C as a companion to GLP-1s, to prevent muscle loss, might get around this shortcoming of GLP-1s, but rigorous research is needed to prove [its effectiveness].

"We hope to generate a better version of MOTs-C and bring it back into clinical development," Cohen says.

1. How should doctors counsel their patients about peptides that have not been FDA approved?

Physicians want to know about their patients' use of unapproved peptides, just as they want to know about any vitamins or other supplements they take.

"We understand that some of our patients may be doing this, and if they are, we'd like to know about it and still be on their health journey with them," says Kumar.

"Then we can order labs and perform other types of tests to be on the lookout for any side effects or any interactions that might pop up," adds Tam. "If there are changes occurring in your body, we can be alert to that."

Doctors should also try to educate themselves on the science that exists, including any safety data, says Kumar.

"I've probably had a dozen patients in the past month who have started the conversation with me about peptides," she says. "I explained to them that there is a lack of quality control, and we don't exactly know about the accuracy of the third-party testing. If peptides are reclassified and allowed to be compounded, then a doctor can write a prescription, but it doesn't make [the substances] FDA-approved, and it doesn't create new data on safety or efficacy."