With massive public interest in weight-loss medications such as semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro), you may be wondering just how they work and how they complement an alternative like Calocurb,® a plant-based natural supplement containing the active ingredient Amarasate, which also curbs appetite.
Production of GLP-1
The common factor for all three weight-loss aids (semaglutide, tirzepatide and Amarasate) is glucagon-like peptide-1 (GLP-1), a hormone that helps regulate blood sugar and increase feelings of fullness by slowing digestion and promoting insulin production.
When we eat, our bodies naturally release GLP-1 from special cells in our intestines; GLP-1 levels rise quickly after eating and then again a bit later. The GLP-1 travels to different parts of our body, like the pancreas and brain, to do its job. However, most of the GLP-1 we make gets broken down quickly by a specific enzyme in our bodies called dipeptidyl peptidase IV, or DPP-4.
GLP-1 receptors
Receptors exist throughout our body, like little docking stations for different molecules. GLP-1 works by attaching to its specific receptors; you can think of them as locks that GLP-1 keys fit into. They’re found in places like the pancreas, gut and brain. When GLP-1 attaches to and activates these receptors, they produce different effects, depending on where the receptors are located.
Effects of GLP-1 receptor activation
GLP-1 has many roles in our body, only some of which are fully understood. Within the digestive system, it slows down stomach emptying, increases insulin production to help regulate blood sugar and helps the liver take up glucose.
In the brain, GLP-1 works to enhance the feeling of fullness (or in technical terms, to “increase satiety”). The delayed stomach emptying and full feeling are basically signals to stop eating, so you can think of GLP-1 as the “you’ve had enough to eat” hormone.
GLP-1 affects how our heart works by increasing heart rate and blood pressure. It may also help our muscles use glucose better and affect fat storage. In addition, there is much interest in other roles GLP-1 may have within the brain, for example, in addictive behaviors.
How Calocurb works
Amarasate, the active ingredient in Calocurb, is made from bitter hops flowers grown in New Zealand. It stimulates the bitter taste receptors in the gut, triggering the release of GLP-1 and other helpful hormones like PYY can CCK. This assists in reducing appetite by increasing satiety through the activation of these natural hormones.
Curiously, taste receptors are not present just on our tongues; they’re found throughout our gut. When activated by Amarasate, the bitter taste receptors produce twice as much GLP-1 as usual. This increase in the natural production of GLP-1 enhances the feeling of fullness and works to reduce your appetite. (When you think about it, it makes evolutionary sense that bitter substances would stop you from eating…back when we were hunter-gatherers, if we ate a bitter plant, it may well have been poisonous, so best not to eat more of it!)
Calocurb should be taken about an hour before eating on an empty stomach and works within the hour. The recommended dosage is one capsule a day, slowly increasing to two capsules before two meals if needed. Some patients may need fewer capsules to feel the effects, either because their bitter taste receptors may be extra-sensitive to Amarasate (producing a even bigger spike in GLP-1) or because their bodies are extra-sensitive to the effects of GLP-1. Others may need to take more Calocurb to feel the full impact and reduce their diet sufficiently to lose weight.
In a study of healthy men, Amarasate’s mode of action was confirmed as being potent stimulation of endogenous production of gut hormones, including GLP-1, cholecystokinin (CCK) and peptide YY (PYY).1 Taken an hour before a meal, this natural supplement combination increased basal levels of GLP-1 and CCK to six times above baseline and to twice the typical release that occurs after eating (Figure 1).1
Moreover, Amarasate enhanced the release of GLP-1 and other hormones in the same physiological pattern seen normally. This resulted in a reduction of caloric intake at subsequent meals of 18% (Figure 2).1 Two further clinical trials demonstrated that Amarasate reduced hunger in fasting men2 and reduced hunger and food cravings in fasting women.3 A subsequent trial is currently enrolling adults with a body mass index (BMI) of at least 30, with a primary endpoint of weight loss following six months of therapy.
Amarasate, the key ingredient in Calocurb, has been clinically proven to reduce hunger by 30%, food cravings by 40% and calorie intake by 18%.
Figure 1. Changes in post-prandial plasma levels of GLP-1 after placebo or Amarasate1
Figure 2. Change in energy intake after Amarasate or placebo an hour before lunch1
Amarasate has few side effects. Some people may experience diarrhea when they start taking it, but this usually goes away and can be reduced by starting it slowly and gradually building up the dose. Nausea is rare with Amarasate.
How GLP-1 receptor agonists work
Weight-loss medications semaglutide and tirzepatide are just two examples of GLP-1 receptor agonists, molecules that mimic natural GLP-1. Some GLP-1 receptor agonists are resistant to the DPP-4 enzyme, while others are animal-derived and are very close to the human molecule. Either way, they work like keys to fit into the GLP-1 receptor locks and activate them. They are primarily injected beneath the skin, after which they flood the body, producing much higher, more constant and longer-lasting synthetic levels than with natural GLP-1.
Note: An oral form of semaglutide is available under the brand name Rybelsus. Whether injected once weekly or swallowed once daily, GLP-1 agonists are often used to treat diabetes by lowering blood sugar. However, these weight-loss medications commonly cause gut side effects, including indigestion, nausea, vomiting and diarrhea; more severe gastrointestinal side effects have also been reported. In addition, they may cause dizziness, headache and a mild increase in heart rate. Around 10% of people in clinical trials stopped using them.
Amarasate’s differences from weight-loss medications
Unlike synthetic GLP-1 receptor agonists like semaglutide and tirzepatide, which are injected and mimic GLP-1, the natural ingredient in Calocurb, Amarasate, stimulates GLP-1 production to 600% above base level.
The very high and constant levels of GLP-1 agonists that occur after weight-loss medications like semaglutide and tirzepatide are injected can explain both their beneficial effects and their unpleasant side effects, for example, activation of part of the brain that makes us feel nauseous. Side effects related to these agents are likely to last for some time, as they are only slowly metabolized in the body. In contrast, Amarasate mimics the natural cycle of GLP-1 production, but at twice the levels that normally occur in response to food intake; this likely explains why it’s less likely to cause nausea compared to other GLP-1 medicines.
Final thoughts on weight-loss medications and natural alternatives
Both Calocurb and pharmaceutical GLP-1 agonists can help restore a healthy weight by slowing stomach emptying and increasing feelings of fullness, thus reducing food intake. Weight-loss medications like semaglutide or tirzepatide can be considered external simulators or mimics of the GLP-1 hormone, whereas Amarasate is a stimulant of our own internal GLP-1.
DCs are recommending Calocurb with Amarasate on its own, in conjunction with GLP-1 agonists or to support patients coming off GLP-1 agonists. Protocols for these three scenarios, as well as others such as menopause, are available by signing up at wholesale.calocurb.com.
SARAH KENNEDY is the founder and CEO of Calocurb.
References
Accessed October 7, 2024
- Walker EG, et al. An extract of hops (Humulus lupulus) modulates gut peptide hormone secretion and reduces energy intake in healthy-weight men: A randomized, crossover clinical trial. Am J Clin Nutr. 2022;115(3):925-940. PubMed. https://pubmed.ncbi.nlm.nih.gov/35102364/#:~:text=Objectives:%20To%20determine%20the%20effect%20of%20a%20bitter%20hop%20extract.
- Walker EG, et al. New Zealand bitter hops extract reduces hunger during a 24 h water only fast. Nutrients. 2019;11(11):2754. PubMed. https://pubmed.ncbi.nlm.nih.gov/31766216/#:~:text=These%20data%20suggest%20that%20appetite%20suppressant%20co-therapy%20may.
- Walker EG, et al. Gastrointestinal delivery of bitter hops extract reduces appetite and food cravings in healthy adult women undergoing acute fasting. Obes Pillars. 2024;11:100117. PubMed. https://pubmed.ncbi.nlm.nih.gov/39071168/#:~:text=Recently,%20gastrointestinal%20delivery%20of%20bitter%20hops%20has%20been