GLP-1 drugs that mimic a hormone called glucagon-like peptide-1 are well-known; they include Wegovy®/Ozempic® and Zepbound®/Mounjaro® and have become famous for helping people lose weight. But there's a lesser-known, non-prescription and natural option that works a bit differently — and a new clinical trial suggests it might have a real advantage: it helps people lose weight without losing muscle along the way.
That option is Amarasate®, a hop extract that's the active ingredient in a supplement called Calocurb®. Here's the interesting part: instead of targeting just one appetite hormone (like GLP-1 drugs do), Amarasate triggers your gut to release three different "feel full" hormones at once.3 And that combination appears to be the reason it preserves muscle mass — something GLP-1 medications are known to struggle with.
This article breaks down what those three hormones actually do, what the latest trial found, and why it matters.
A Quick Word on How Appetite Hormones Work
Your gut isn't just a digestion tube — it's actually one of the largest hormone-producing systems in your body. Specialized cells lining your intestines, called enteroendocrine cells, make up only about 1% of your gut lining but form the largest endocrine (hormone-producing) system in the human body.4 These cells carry various receptors for different substances (bitter or sweet ones, proteins, fats, etc) to sense what you're eating and, in response, release hormones into your bloodstream and along dedicated nerve pathways that connect straight to the vagus nerve — your body's main gut-to-brain highway.5 The message these hormones send to your brain is often simply: "you've had enough" or "slow down."
This is exactly the system that GLP-1 drugs exploit — they mimic one of these natural hormones (GLP-1) to turn down appetite. Amarasate works differently: rather than being a synthetic copy of a hormone, it's a very bitter plant compound that stimulates your own gut cells to release hormones — and it turns out it nudges the release of three, not just one.6 These gut cells vary somewhat from person to person and region to region,7 and because scientists are still refining exactly how to classify them,89 researchers are still learning the full picture — but the effects of Amarasate on these three hormones specifically have now been measured directly.
Meet the Three Hormones
GLP-1 — the one you've probably heard of
GLP-1 is the hormone that semaglutide (Ozempic/Wegovy), and similar drugs are designed to imitate. Natural GLP-1 is released after eating and tells your brain you're satisfied, while also slowing down how fast your stomach empties, so fullness lasts longer.
In the research, a single 500 mg dose of Amarasate increased people's natural GLP-1 levels to 640% of their normal baseline — comfortably above the roughly 4-fold increase scientists believe is needed to actually reduce how much someone eats.1011 That's a big part of why it works. It's also worth noting that Amarasate itself is barely absorbed into the bloodstream (less than 1.5%), which means it keeps working all the way down the length of the gut, including areas food alone wouldn't typically reach with this kind of signal.12
CCK — the one that helps you digest, feel full, and burn energy too
CCK (cholecystokinin) probably isn't a hormone you've heard of, but it's a heavy lifter. It's released mainly in response to fat and protein in a meal, and it does double duty:
- In your gut: it tells your gallbladder to release bile (which helps digest fat), slows stomach emptying, and helps you absorb protein.13
- In your brain: it sends direct signals of fullness, and it works together with another hormone, leptin, to reinforce that "I'm satisfied" feeling and burn energy (thanks, leptin!).14
CCK may also help burn fat in a few other indirect ways, based on lab and animal studies. It raises levels of a hormone called adiponectin,15 which helps the body burn fat for energy, supports healthy fat storage, and keeps fat from building up in places it shouldn't (like the liver).161718 CCK also boosts a hormone called leptin, which does more than just tell your brain you're full — it also acts directly on fat tissue to break down stored fat, encourage the body to burn it for fuel, and reduce the creation of new fat.19 On top of that, lab studies suggest CCK can help turn regular white fat into a more active, calorie-burning type of fat, sometimes called "beige fat."2021
It's worth noting that none of these individual effects have been proven, on their own, to cause meaningful weight loss in human studies. But together, they may help explain some of the fat-burning results seen in the Amarasate study, where CCK levels were increased.
Amarasate increased CCK levels 600% in the same study — again, well above the roughly 3.6-fold threshold thought necessary to reduce food intake.2223 There's also a knock-on benefit: the bile that CCK triggers can itself stimulate more GLP-1 release further down the gut, so the hormones reinforce each other.24
PYY — the one that may protect your muscle
PYY (peptide tyrosine tyrosine) is the least talked-about of the three, but it may be the most important piece of this particular puzzle. PYY is normally released after eating, especially after high-protein or high-fat meals (though this response is somewhat blunted in people who are obese).25 Like GLP-1 and CCK it has effects within your brain to help put the brakes on your appetite and also slows down digestion — sometimes called the "colonic brake," because it also smooths out blood sugar spikes after meals.2627
But here's the part that's caught researchers' attention: PYY receptors have also been found on skeletal muscle itself and on the stem cells responsible for repairing and building new muscle fibers.28 In other words, PYY doesn't just talk to your brain — it may also talk directly to your muscles, helping them repair and adapt rather than break down.29 Levels of PYY inside muscle tissue rise during low-energy states (like when you're eating less to lose weight), which hints that your body may lean on PYY to help protect muscle when it's under that kind of stress.30
Amarasate raised PYY by 1.7 times in the initial study — a smaller bump than GLP-1 or CCK, and short of the roughly 3-fold threshold thought to directly reduce food intake on its own.3132 But researchers believe it may still be meaningful, especially in combination with the other two hormones, and especially for muscle preservation over time.
By increasing levels of these three "stop eating" hormones, Calocurb acts as an all-natural "bitter brake", helping people feel full faster and for longer, and reducing how much they eat.
- Activates brain appetite control centres
- Slows down stomach emptying
- Activates brain appetite control centres
- Slows down stomach emptying
- Stimulates leptin release from fat cells
- Aids in fat digestion
- Activates brain appetite control centres
- Slows down stomach emptying
- Involved in repair and growth of muscle fibres
What the Latest Study Actually Found
The headline result comes from a 24-week, placebo-controlled trial of 150 people.33 Participants took two 125 mg Calocurb capsules about an hour before their two largest meals each day. Here's what happened, compared with the placebo group:
| What was measured | Calocurb (Amarasate) | Placebo |
|---|---|---|
| Average weight loss | 4.8% | 0.5% |
| Weight loss adjusted for muscle change | 5.3% | 0.7% |
| Change in muscle mass | Gained 2.0 lb / 0.9 kg | Gained 0.4 lb / 0.2 kg |
Table 1: 24-week trial outcomes — Calocurb (Amarasate) vs placebo. Walker E et al., Obes Pillars, 2026.
Both differences in weight loss were statistically significant, meaning they're unlikely to be due to chance.34 Side effects were minimal — in fact, only one person in each group (treatment and placebo) dropped out because of side effects, which is a notably low number for a weight-loss study.35
To put the muscle result in context: with most weight-loss approaches — and especially with GLP-1 medications — somewhere between a quarter and a third of the weight lost is actually muscle, not fat. That's a real concern, because losing muscle can slow your metabolism, weaken you physically, and make it harder to keep weight off long-term. Amarasate users, by contrast, at the very least, maintained their muscle, on top of losing fat.36
So Why Does It Protect Muscle When GLP-1 Drugs Don't?
This is really the heart of the story. Researchers believe the answer lies in the PYY, one of the two extra hormones GLP-1 drugs don't touch.
There's also a related clue: people with sarcopenia (age- or illness-related muscle loss) tend to have higher GLP-1 levels, and lab studies suggest GLP-1 plays a role in normal muscle repair.37 That may partly explain why long-term GLP-1 drug use is associated with muscle loss — it's a synthetic, one-note version of a hormone system that naturally works as a trio. Amarasate, by stimulating all three hormones together the way your body would naturally, seems to sidestep that downside.
How Might This Be Used?
Because Amarasate works through a different (and broader) mechanism than GLP-1 drugs, it's being explored in a few different roles:
As an alternative to GLP-1 medication, for people who prefer a non-prescription option or can't tolerate the drugs.
As an "off-ramp" for people coming off GLP-1 medications, to help maintain results.
As a complementary add-on taken alongside GLP-1 drugs, specifically to help counter the muscle loss and the drop in the body's own GLP-1 production that can come with long-term use.38
Natural appetite support
Three hormones. One capsule.
Calocurb contains Amarasate, the only clinically studied ingredient shown to stimulate GLP-1, CCK, and PYY simultaneously — supporting appetite control and muscle preservation naturally.
