From Hops to Healing: A Natural Compound Moves Patients with Crohn's Disease Toward Remission in Phase 2 Trial

Crohn’s disease is a chronic inflammatory condition of the gut that affects roughly 1.5 million Americans. It brings unpredictable flares of pain, fatigue, and digestive distress, and treatment choices often feel like picking between bad options.

Corticosteroids can tamp down inflammation during a flare, but their side effects are serious enough that doctors can only prescribe them short term. Biologic therapies like Humira and Remicade are powerful but expensive, out of reach for many patients, and they don’t work for everyone. Even when the therapies do work, they can lose their effectiveness over time. For people living with Crohn’s, the daily reality is a disease that demands constant management with medications that fall short.

“If you ask patients, they are not happy with current treatments,” says Dr. Fred Stevens. Stevens is the Institute’s Ava Helen Pauling Chair and a professor in the Oregon State University College of Pharmacy.

His research team set out to find something better. And after more than a decade of meticulous research — from cell cultures to animal models to a completed phase 2 clinical trial — there is real reason to believe they have.

A Natural Compound That Goes Where It’s Needed

Xanthohumol is a compound found in hops. What makes it unusually well-suited for a gut disease is simple: very little passes from the intestine into the bloodstream. That sounds like a limitation, but for Crohn’s disease, it’s an advantage. Because most of an oral dose stays in the intestinal tract, xanthohumol reaches the exact tissues where Crohn’s does its damage — the lower small intestine and the beginning of the colon.

Once there, preclinical research in the Stevens laboratory shows that xanthohumol does four things that matter for patients. Xanthohumol: 

• Strengthens the intestinal barrier that Crohn’s weakens.
• Reduces inflammation.
• Supports the growth of beneficial gut bacteria while inhibiting harmful ones. 
• Targets the core mechanisms that drive the disease, not just the symptoms.

Testing It Where It Counts: In Patients

What works in the lab doesn't always work in people, and getting the chance to find out is itself a milestone that takes years of evidence to reach. The Xanthohumol Microbiome and Signature trial — the XMaS trial — put xanthohumol to that test. A Phase 1 study with 30 enrolled adults confirmed safety and tolerability. Phase 2 honed the research by enrolling 19 adults with clinically active Crohn's disease — all with elevated disease activity scores.

In this randomized, triple-masked, placebo-controlled trial, one-half of the participants received 24 mg per day of xanthohumol; the other half received a placebo. Already four weeks into the study, the results were striking. Xanthohumol-treated patients with elevated markers of inflammation saw their disease activity scores fall to levels consistent with remission. The improvement was significantly different from the placebo-treated patients. The xanthohumol-treated patients remained in remission until the end of the study in week 8.

The treatment also suppressed the production of secondary bile acids — harmful compounds generated by gut bacteria that, in the presence of active inflammation, exacerbate intestinal damage. This confirmed a mechanism that the Stevens' team had identified in preclinical work: xanthohumol inhibits bile salt hydrolase, the bacterial enzyme responsible for producing these bile acids.

And perhaps most meaningful for the patients themselves: xanthohumol produced no detectable toxicity and no adverse events.

What This Could Change For People Living With Crohn’s

This is where the human impact comes into sharpest focus. If further trials confirm these findings, xanthohumol could offer patients something that none of the current options do: a treatment that is safe enough to take every single day, for the long term, without the side effects that make existing therapies so difficult to live with.

“The safety profile of xanthohumol is much more favorable compared to corticosteroids,” Stevens said. “I’m thinking you can take it all the time. That is a big advantage.”

It is also inexpensive — a stark contrast to biologic therapies that can cost tens of thousands of dollars per patient per year. It is the difference between a treatment that exists on paper and one that patients can actually access. The economic burden of Crohn’s disease not only hits patients’ pockets for these expensive medications but also causes multiple periods of disability and lost days of work or school throughout their lifetime.  

Xanthohumol’s potential benefits may extend well beyond Crohn’s. The underlying features of the disease — chronic inflammation, a disrupted microbiome, a compromised intestinal barrier — are shared by ulcerative colitis, metabolic syndrome, and a range of other conditions that affect millions more people.

Earlier work in the Stevens lab using animal models showed that xanthohumol improved markers of metabolic syndrome by reshaping the gut microbiome and reducing inflammation. The science suggests that what works for Crohn’s may work much more broadly, keeping in mind that baseline inflammation is a prerequisite for benefit. 

Made Possible by Sustained Support

Research like this does not happen in a straight line, and it does not happen without sustained investment. The path from a promising molecule to a clinical trial that changes patients’ lives takes years of fundamental science, infrastructure, and belief that rigorous work will eventually benefit the people who need it most. Philanthropic support makes that long road possible. To support research like this, visit lpi.pub/SupportLPI for options such as the Research Innovation Fund.