Successful weight management is now a global health concern as more than 43% of adults are categorized as overweight or obese. Long term weight management requires lifestyle modification but often includes higher-force interventions such as pharmaceutical or surgical care. Pharmaceutical interventions are usually designed to reduce food intake by manipulating appetite; however, these interventions have long-term feasibility or safety concerns. Naturally derived compounds, with favorable safety profiles and the ability to powerfully suppress appetite and cravings, represent an appealing option for ongoing weight management.

Appetite regulation is orchestrated by a complex network of physical and chemical signals, with enteroendocrine hormones serving as some of the most powerful drivers of hunger and satiety. Under normal physiology, orexigenic hormones such as ghrelin rise during fasting and between meals, while anorexigenic hormones including GLP-1, CCK and PYY are released after eating. Specialized enteroendocrine cells in the gastrointestinal tract release these hormones in a dose- and time-dependent manner in response to nutrient intake.

In 2010, the New Zealand government funded a large grant to investigate the appetite suppressive effects of bitter plant compounds as a potential treatment option for weight management. After investigating over 1,000 different plant compounds in vitro, the researchers concluded that a native New Zealand hops extract produced the strongest TAS2R stimulation and consequential enhanced release of anorexigenic (GLP-1, CCK and PYY) hormonal response, indicating the strongest appetite suppressant effect. The researchers named the extract Amarasate^®, derived from Latin, meaning “bitter satiation.”

Patients should begin Calocurb^® CLINICAL using the Starter Pack. This pack onboards the body to the increased activation of natural satiety hormones, preparing it for the higher doses of the Calocurb^® CLINICAL Maintenance Pack (coming soon).

In 2019, the first clinical study on Amarasate^® was conducted in a randomized, double-blind trial investigating its appetite suppressive effects during a 24-hour, water-only fast. Participants given Amarasate^® or placebo at hours 16 and 20 were evaluated for hunger and satiety with a standard visual analog scale (VAS) every 30 minutes after capsule administration. Amarasate^® participants reported an 80% reduction in hunger elevation scores compared to the placebo group. In a comparable water-fast study conducted in women, Amarasate^® supplementation led to a 100% suppression of hunger elevation and a 120% reduction in food cravings relative to placebo.

A more expansive study of adult men sought to correlate the subjective reduction in hunger from the first study with anorexigenic biomarkers, specifically GLP-1, CCK and PYY. The study also sought to investigate which was more efficacious, intragastric or intraduodenal delivery of Amarasate^®. In the randomized, double-blind study, the subjects were given either placebo, intraduodenal Amarasate^® (delayed-release capsule), or intragastric Amarasate^® (immediate-release capsule) one hour before an ad libitum meal and subsequent snack. Both Amarasate^® delivery methods had significant elevations in GLP-1, CCK and PYY; however, the intragastric capsule also had significantly more adverse events than the intraduodenal capsule likely due to the high amount of TAS2R bitter receptors in the stomach. Intraduodenal delivery of Amarasate^® resulted in 600% elevation from baseline of GLP-1 and CCK, and 50% elevation of PYY.

CLINICAL CONSIDERATIONS

Amarasate^® is a potent and effective appetite modulator, offering a targeted approach to supporting satiety and caloric control. It can be used independently or integrated into a comprehensive strategy for weight loss or maintenance. Calocurb^® CLINICAL may be co-administered with weight-loss medications to help manage breakthrough hunger or used during medication tapering to support appetite control. Alternatively, Calocurb^® CLINICAL can also be used as needed to support adherence to time-restricted eating or to help manage appetite and craving increases that may occur premenstrually.