Their blood looked like the blood of elite endurance athletes.
Somewhere in the blood of men running ultramarathons, researchers found a molecule that seemed to explain part of what exercise does to the body — a compound called N-lactoyl-phenylalanine, or Lac-Phe, that rises sharply during intense physical activity and appears to suppress appetite and help regulate weight. That discovery was interesting enough on its own. What happened next was unexpected.
When scientists looked at prostate cancer patients being treated with metformin — a decades-old diabetes medication so common it's practically generic — they found Lac-Phe levels that matched those of the ultramarathon runners. Men who weren't running anywhere. Men who, in many cases, were dealing with the metabolic fallout of hormone therapy. Their blood looked, in this one specific way, like the blood of elite endurance athletes.
"We were very surprised," said Marijo Bilusic, the study's lead author and a genitourinary oncologist at Sylvester Comprehensive Cancer Center. He and his team had been asking a pointed question: cancer is defined in part by altered metabolism, so what happens when you give a metabolic drug like metformin to cancer patients? The Lac-Phe finding, he noted, had never been reported before in this context.
The research, published April 6 in the journal EMBO Molecular Medicine, drew on two groups of prostate cancer patients. The first came from a clinical trial called BIMET-1, where 12 men with overweight or obesity — none of them diabetic — were studied in detail out of 29 originally enrolled. They were randomly assigned to standard care or metformin at 1,000 mg twice daily, followed by the hormone therapy drug bicalutamide. The second group included 25 additional prostate cancer patients across various disease stages, seven of whom were taking metformin. Across both groups, the team measured Lac-Phe before and after treatment.
The results were consistent. Metformin raised Lac-Phe levels regardless of cancer stage, body weight, or what other treatments patients were receiving. In the clinical trial group, the increase after metformin was significant. In the broader group, those on metformin had clearly higher levels than those who weren't. And crucially, the men on metformin also fared better on weight. Nearly all of them avoided gaining weight during hormone therapy — a treatment notorious for causing exactly that. Those not on metformin were more likely to put on pounds.
This matters because hormone therapy for prostate cancer, particularly anti-androgen drugs, is strongly associated with weight gain, metabolic syndrome, and elevated cardiovascular risk. Managing those side effects is a real clinical problem, and exercise — the obvious intervention — isn't always accessible to men who are ill, fatigued, or otherwise limited. The idea that a cheap, well-understood drug might partially replicate one of exercise's metabolic effects is worth taking seriously, even if the mechanism isn't fully understood. Lac-Phe is thought to act on the brain to reduce appetite and food intake, but exactly how remains an open question.
One thing the study did not show: metformin did not improve cancer outcomes. PSA levels, tumor progression, and treatment response were unaffected. This aligns with the STAMPEDE trial, a large prospective study published in 2025, which found metformin helped with weight and glucose control in prostate cancer patients but showed no survival benefit. The drug appears to be doing something metabolically useful without touching the cancer itself.
S. Adam Ramin, a urologic oncologist in Los Angeles who was not involved in the research, described the study as intriguing but preliminary. He pointed out that men on hormone therapy are at real risk of developing obesity and metabolic complications, and that metformin might eventually prove useful in preventing those outcomes. But he was careful to add that recommending it broadly to prostate cancer patients on hormone therapy would be premature at this stage.
The study is small, and the researchers know it. What they've produced is a hypothesis with a compelling biological signal behind it — not a treatment protocol. The next step is larger trials that can test whether the Lac-Phe connection holds up at scale, and whether the weight benefits translate into meaningful reductions in cardiovascular risk or other complications. For now, the finding sits at the edge of what's known: a diabetes drug, a molecule born in the muscles of runners, and a group of cancer patients whose blood told a story nobody had seen before.
Notable Quotes
The level of Lac-Phe in our prostate cancer patients was exactly the same as the level of ultramarathoners. This has never been reported before.— Marijo Bilusic, MD, PhD, lead study author and oncologist at Sylvester Comprehensive Cancer Center
At this point, it is premature to recommend metformin to patients with prostate cancer on hormone therapy.— S. Adam Ramin, MD, urologic oncologist and medical director of Urology Cancer Specialists, Los Angeles
The Hearth Conversation Another angle on the story
What's actually new here — metformin has been around forever.
The novelty is the molecule. Lac-Phe was only recently identified as something the body produces during exercise, and nobody had looked for it in cancer patients on metformin before.
And the levels really matched ultramarathon runners?
That's what the researchers found, and they were surprised by it too. These weren't athletes — they were men in cancer treatment.
Does that mean metformin is basically exercise in a pill?
Not even close. It seems to mimic one specific downstream effect — this appetite-suppressing molecule — but exercise does dozens of things at once. This is one thread, not the whole fabric.
So why does it matter for prostate cancer specifically?
Because hormone therapy, which many of these men are on, causes weight gain and metabolic problems almost as a rule. If metformin can blunt that, it addresses a real quality-of-life issue.
Did it help the cancer itself?
No. PSA levels, tumor response — none of that moved. The drug seems to be working on the metabolic side effects, not the disease.
How many people were actually in this study?
Small numbers — 12 in the main trial group, 25 in a broader confirmation group. That's why everyone involved is calling it exploratory.
What would it take to actually change clinical practice?
Larger randomized trials that can show whether the weight benefit holds up and whether it translates into fewer cardiovascular events or other complications down the line.
Is anyone already prescribing metformin off-label for this?
The researchers aren't recommending it yet, and the outside expert quoted in the study was explicit that it's too early. The signal is interesting; the evidence base isn't there yet.