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From mice to ‘gym rats’: Unregulated use of peptides raises alarm among researchers

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From mice to ‘gym rats’: Unregulated use of peptides raises alarm among researchers

A few months ago, Pinchas Cohen learned of a thriving online trade in MOTS-c — a peptide that, when injected into mice, seems to mimic the effects of exercise.

The dean of the USC Leonard Davis School of Gerontology was very familiar with this particular short chain of amino acids. His lab identified it years ago as one of the thousands of peptides that act as chemical messengers in the human body, one he believed might someday have therapeutic uses for humans.

But Cohen was alarmed to learn that his discovery was now being promoted by legions of longevity seekers, fitness enthusiasts and wellness influencers as “exercise in a bottle.” Though not approved by the U.S. Food and Drug Administration, it was widely available online, often in vials marked “for research use only.”

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“Turns out that tens of thousands of people are injecting themselves with MOTS-c [that’s] black market, illegal, from unknown sources, unknown purity, unknown sterility, and I strongly object to that,” Cohen said.

Driven by social media hype and a growing distrust of public health guidance, consumer demand for experimental peptides has exploded over the last decade. Now, the clamor over unregulated peptides is fueling a high-stakes policy battle within the federal government. Health and Human Services Secretary Robert F. Kennedy Jr. has described himself as a “big fan” and user of peptides, and has pledged to end the government’s “aggressive suppression” of them.

Some peptides, such as insulin, human growth hormone and glucagon-like peptide-1, have delivered transformational therapeutic effects when administered to humans.

But every vial of insulin or GLP-1 medication on a pharmacist’s shelf is the product of decades of clinical trials and safety testing. There are reams of data on what these drugs do, for whom they are most effective and in what dose and form they should be administered.

For MOTS-c and a raft of other peptides widely available online, no comparable evidence exists.

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Although proponents say the substances help with weight loss, energy and muscle mass, and often cite research that has been done solely on animals or on a very small number of humans, no one knows for certain how or when it should be used in humans. While many users take multiple peptides together in custom combinations, or “stacks,” there is no data on how different synthetic peptides interact with one another.

To date, most of these popular peptides have been available solely in unregulated online marketplaces. But recently, an FDA committee voted to recommend that compounding pharmacies be allowed to manufacture six different peptides already widely available online: BPC-157, TB-500, KPV, epitalon, Semax and MOTS-c. A seventh, emideltide, was voted down.

Compounding pharmacies, which mix bespoke drugs, are a loophole in the U.S. regulatory system. While the drugs they produce aren’t FDA-approved, the pharmacies still have to follow their state’s safety and quality regulations.

Cohen traveled to Washington, D.C., to speak before the committee, many of whose members work for the kind of telehealth, longevity and wellness companies that stand to benefit financially from the peptides’ regulation.

Given that MOTS-c is already widely used off-label and no research has shown evidence of harmful side effects, Cohen said in his remarks that he believed “quality-controlled, prescriber-supervised” compounding was the safest way forward.

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“We can’t stop the black market. So I think it’s a better choice to at least guarantee the quality, the sterility, and require that real doctors are part of the process,” he said later. “I really think this is a better choice than just letting it go on the way it is.”

Not everyone agrees with him. FDA staff who spoke at the two-day meeting advised against peptide compounding, saying there was not enough safety data to justify the move.

The vote is non-binding, and the FDA could choose to side with its own scientists.

“My impression is that the ‘lesser of two evils’ argument is a minority perspective,” said Paul Knoepfler, a cell biology and human anatomy professor at the UC Davis School of Medicine who writes frequently on peptides.

“While it’s true that most compounders can likely [produce] purer versions of these peptides than what’s in the gray market, that doesn’t address potential inherent risks of the peptides themselves,” Knoepfler said. “There’s no special reason they should be allowed to bypass the standard clinical trial system just because there’s a peptide fad driven by wellness influencers and telehealth firms.”

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Cohen found MOTS-c by combing through the 97% of human DNA that doesn’t encode for genes. This biological hoard once dismissed as “junk DNA” or the “dark genome” has turned out to be full of hormones and microproteins that play important roles in directing the body’s systems and processes.

Roughly 250 papers from dozens of research labs around the world have been published on MOTS-c since Cohen’s lab identified it. While the peptide’s risks and side effects are few, and its effects on mouse metabolism compelling, no one knows how long-term use affects humans yet, or what formula or dosage would be most effective. Influencers’ claims about the peptides’ effect on human weight loss, muscle mass, longevity and energy appear to be extrapolated from their effects on lab animals.

“Certain groups of people — for example, the fitness enthusiasts, which is the kind way to refer to gym rats — those people take one figure from one paper done on mice and take it to become gospel,” Cohen said.

Many users have been happy to essentially volunteer themselves for further testing.

“Today I used Mots-c for the first time and I’m a believer,” a Reddit user posted earlier this year. “I did some outdoor sports for about an hour and then came home and spent several hours doing every chore that had been piling up all week.”

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The reality is more nuanced. For scientists like Cohen, these molecules are an exciting area of research that could reap significant health breakthroughs. But rigorous science takes time, and they’re up against a public that has lost patience with the traditional drug approval model — and a market that is happy to provide alternatives.

In an ideal world, Cohen said, he would like to see MOTS-c developed into an FDA-approved drug. But in the actual world, taking a single drug from the lab to the market requires so much time (at least 10 years, usually more) and money (at least hundreds of millions of dollars, usually more) that very few candidates successfully reach that goal. His own efforts to move MOTS-c through the development pipeline stalled.

“Peptides are neither miracle cures nor snake oil. They are signaling molecules. Some have strong evidence. Some have intriguing or early data. Some are wildly overhyped, and some probably should never leave the laboratory,” said Dr. Ben Gonzalez, a former emergency medicine physician at Walter Reed Army Medical Center, at the FDA meeting. “Patients are looking for alternatives, and they are looking not at physicians. They’re looking at this gray market source.”

If compounded peptides are ultimately approved, Cohen would like to start an online registry where patients can anonymously record the dosage they’re taking, the reason they’re taking it and any side effects they experience, so that scientists can collect some data on this real-world experiment.

“The big picture is that we’re transitioning as a nation from the 20th century model [in which] all healthcare was dictated by physicians and insurance companies to a new 21st century model where consumers are demanding and receiving health and wellness services and products that they pay for in cash,” Cohen said. “I’m not saying that’s a better model. But it’s the model we’re transitioning into.”

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Rare Mastodon Tooth Found in California Creek

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Brigid Lynch, a geologist, was conducting a field survey in San Mateo County, Calif., when she saw a strange object sticking out from the creek. After a reverse Google image search, and an expert’s confirmation, she learned she had found a Pacific mastodon molar.

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California’s biggest lake is in crisis. Now tribes are coming back to save its sacred fish

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California’s biggest lake is in crisis. Now tribes are coming back to save its sacred fish

Jose “Moke” Simon III recalls as a child in the ‘70s watching the creeks that flow into Clear Lake in Northern California turn black with fish — a fish found only in these waters — as they made their springtime run.

Someone would call from the neighboring reservation with the news: “The hitch are running!” Everybody would grab their ice chests and pile into cars.

“They ran so thick in the rivers, you didn’t even need a pole,” said Simon, now chair of the Middletown Rancheria of Pomo Indians. “You’d just get in there and splash them out of the river, or catch them in your shirt.”

But those days are gone. As Clear Lake, which sits in Lake County, north of Napa, faces mercury contamination, toxic algal blooms and predatory invasive fish, the Clear Lake hitch — known by local tribes as the chi — are in serious trouble. Another fish unique to the watershed, the Clear Lake splittail, is already extinct.

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After years of advocacy and on-the-ground work to save the fish, the seven tribes around the lake signed an agreement with state agencies and local governments Friday to formally co-manage the troubled body of water. Nearly two centuries after Europeans took over these lands, it’s a literal watershed: the first agreement governing a watershed since the state launched an initiative to bring 7% of California’s lands and waters under the care of tribes.

Native Americans perform during an event at Clear Lake, where seven tribes signed on with state agencies and local governments to formally co-manage the Clear Lake watershed, the first agreement of its kind under a new state tribal stewardship initiative.

(/Calif. Natural Resources Agency)

The tribes hope it will turn their ad hoc emergency work — which has coincided with an increase of chi in the lake — into a lasting strategy to protect the fish.

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“I really hope it’s going to solidify the long-term success and vitality of this fish for the next seven generations,” Simon said, who described the signing as the most government agencies he’s ever seen come together in the region.

As far back as stories go, the chi have been vital for the region’s Indigenous people. Every year, Pomo nations would gather at the south end of the lake to catch and dry the fish that would sustain them throughout the year, Simon said.

But nearly two centuries ago, European settlers started fracturing this relationship.

Settlers began arriving by the 1840s. A pair of particularly brutal white ranchers enslaved and starved Pomo villagers, murdered men on a whim and raped women and children. Eventually, the Indigenous locals rose up and killed them. In response, on May 15, 1850, armed vigilantes and the U.S. Army slaughtered hundreds of tribal members.

The following year, the U.S. government promised the tribes reservations but failed to create them. What they got instead, decades later, were much smaller “rancheria” reservations that the government again terminated in 1950s. Without oversight of the land, protecting the chi has been an upstream battle.

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“We don’t own the land, but we certainly feel like we have an immense responsibility to be good stewards and caretakers of the land,” said Danielle Cirelli, chair of the Habematolel Pomo of Upper Lake.

As for fish, settlers had begun introducing nonnative species by the late 1800s for sport fishing. They proved to be invasive. Today there are more than 20 introduced species still in the lake that kick up sediment, destroy the plants the chi live among and eat their eggs.

A view of milky way during a meteor shower at Clear Lake in 2024.

A view of milky way during a meteor shower at Clear Lake in 2024.

(Tayfun Coskun / Anadolu via Getty Images)

In the 1920s, a modest mercury mine grew into a large open-pit operation, contaminating the watershed with the toxic metal. The mercury made its way into the fish, posing a risk to tribal members who relied on the chi for food.

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To make matters worse, Clear Lake has struggled with dramatic blooms of toxic algae, spurred by stretches of hot summer days with little wind. As the warm water sits still at the top, oxygen no longer circulates to the bottom. This sets off a chemical reaction freeing phosphorus, a primary nutrient for the algae, from the lake floor. The heat, low oxygen and toxic algae all harm the chi.

Globally, these kinds of blooms are increasingly common as human-caused emissions continue to warm the Earth.

It’s “death by a thousand cuts,” said Steve Sadro, UC Davis environmental science and policy department chair who works on Clear Lake rehabilitation.

In 2017, Clear Lake’s dire condition led the state to establish a blue ribbon commission, with tribal participation, focused on cleaning up the lake to bolster the local boating and fishing economy. But drought struck the region in the early 2020s — shrinking the streams where the chi spawn. The tribes began sounding the alarm and the state set up a Clear Lake Hitch Task Force with the tribes.

The result has been a surge of activity in recent years, much of it spearheaded by the tribes.

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UC Davis developed a device that pumps oxygen from a tank onshore to the bottom of the lake to combat the algae problem. The Big Valley Band of Pomo Indians monitors water quality for algal blooms and cleans up spawning creeks that get clogged with sediment and trash.

The Robinson Rancheria of Pomo Indians tracks and removes invasive fish like carp and goldfish and now plans to start setting fire to tule — a giant grass-like plant that the chi rely on for shelter — to help it grow better. The Habematolel Pomo of Upper Lake catch and tag the chi to better understand their behavior.

The tribes also have worked together after rains to orchestrate rescue missions for chi that are trapped in puddles, offshoots and agricultural ditches.

“This co-management agreement is really putting pen to paper on what is already happening on the ground,” said Geneva E.B. Thompson, deputy secretary for tribal affairs at the California Natural Resources Agency. It’s “a beautiful example of what shared decision-making can look like for a watershed, for a fish species.”

Simon hopes it moves the tribes one step closer to freely catching the chi again, like he did as a child.

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“That would be something to see,” he said, “before I’m back in the earth.”

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Artemis II astronaut and SoCal native Victor Glover steps back from NASA, joins Cal Poly

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Artemis II astronaut and SoCal native Victor Glover steps back from NASA, joins Cal Poly

Astronaut Victor Glover, a Southern California native who piloted NASA’s Artemis II mission around the moon this year, is stepping back from the space agency.

He began a full-time leadership position at his alma mater, Cal Poly in San Luis Obispo, on Sept. 1, according to a news release from the university.

As the only pilot to have flown NASA’s moon-faring Orion capsule, Glover will continue supporting astronaut training for lunar missions under the agency’s emeritus program, according to a NASA news release.

Glover’s crewmate, Artemis II cmdr. Reid Wiseman is also retreating from astronaut duties to join the emeritus program, the agency said. Artemis II mission specialist Jeremy Hansen announced in July he would step back from the Canadian Space Agency this month.

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Out of the crew of four, that leaves only mission specialist Christina Koch as a full-time astronaut.

In June, Glover visited Cal Poly to speak to an audience of nearly 1,300 about his experience flying around the moon. In August, he made a surprise appearance on campus around the start of fall classes at a welcome event for students and families at the university’s stadium.

In his new role, the astronaut will work closely will Cal Poly’s president to position the university as a “global leader in polytechnic education, research innovation and workforce production,” the news release said. He will also work on initiatives to “inspire the next generation of students to pursue STEM-related disciplines.” (STEM stands for “science, technology, engineering and math.”)

Cal Poly has always held a special place in Glover’s heart. He met his wife, Dionna, on campus while both were students. All four of his daughters have either graduated or are attending the university.

Glover was born in Pomona and graduated from Ontario High School. During his upbringing, he lived “all over” Southern California’s urban sprawl, including Baldwin Village. He graduated Cal Poly in 1999 with a degree in engineering.

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After serving in the military for 15 years — including as a Navy test pilot — he was selected by NASA for its 21st class of astronauts in 2013.

At the space agency, he piloted the first operational mission of SpaceX’s Crew Dragon capsule to the International Space Station in 2020. In April, he piloted NASA’s first mission to return humans to the moon in more than 50 years.

While the Artemis II crew did not land on the lunar surface, the astronauts’ expressions of awe for the lunar surface and profound love for Earth captured the public’s attention.

“Maybe the distance we are from you makes you think what we’re doing is special,” Glover said on Easter while on his way to the moon. “But we’re the same distance from you, and — I’m trying to tell you, just trust me — you are special. In all of this emptiness — this is a whole bunch of nothing, this thing we call the universe — you have this oasis, this beautiful place that we get to exist, together.”

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