by Benjamin Bikman, PhD
How GLP-1 works
Glucagon-like peptide-1 (GLP-1) is a hormone that plays a pivotal role in regulating glucose metabolism and appetite. Derived from the proglucagon gene, GLP-1 is primarily secreted by the L-cells in the small intestine in response to nutrient ingestion, including certain carbohydrates, proteins, and fats. Interestingly, it is also produced in smaller amounts by the pancreas and central nervous system. The discovery of GLP-1’s functions and its potential therapeutic uses was significantly advanced through studies on patients who had undergone gastric bypass surgery. These patients exhibited rapid improvements in glucose homeostasis and weight loss, which were linked to increased secretion of GLP-1 and other incretin hormones. Naturally, scientists began to wonder: How much of the metabolic benefit is a result of increased GLP-1?
Favorable metabolic effects of GLP-1
In its earliest uses, GLP-1 worked to lower blood glucose levels by inhibiting the hormone glucagon. Whereas insulin acts to lower blood glucose, glucagon acts to increase blood glucose. Thus, if glucagon were reduced, glucose would follow, helping to maintain blood glucose levels within a normal range. With further study, GLP-1 was also found to slow gastric emptying, which moderates the release of nutrients into the bloodstream, preventing spikes in blood glucose levels and promoting greater satiety (i.e., if food moves more slowly through your intestines, you will feel fuller). Additionally, GLP-1 acts on the central nervous system to promote satiety and reduce appetite. These combined effects make GLP-1 a powerful regulator of metabolism and a potential tool for managing conditions like type 2 diabetes and obesity (Flint et al., 2001).
GLP-1 and appetite regulation
GLP-1 significantly influences appetite by acting on brain regions involved in hunger and reward. Studies have shown that GLP-1 infusion can reduce food intake and increase feelings of fullness. For example, in a study involving obese men, an eight-hour GLP-1 infusion reduced hunger ratings and decreased energy intake by approximately 21% (Näslund et al., 1999). Functional MRI studies have further demonstrated that GLP-1 receptor activation modulates brain regions associated with appetite and reward, such as the insula and amygdala, reducing the appeal of food (van Bloemendaal et al., 2014).
Therapeutic use of GLP-1
Given the myriad metabolic benefits of GLP-1, it’s no surprise that drug companies have sought to leverage its effects. GLP-1 receptor agonists, such as exenatide and liraglutide, are the drugs based on GLP-1 that are used to treat type 2 diabetes and obesity. These drugs mimic the effects of natural GLP-1, inhibiting glucagon, slowing gastric emptying, and suppressing appetite. Clinical studies have shown that these medications can lead to significant weight loss and improved glycemic control in patients with type 2 diabetes (Toft-Nielsen et al., 1999).
Negative effects of GLP-1–based drugs
However, despite their benefits, GLP-1 receptor agonists are not without side effects. Common adverse effects include nausea, vomiting, and diarrhea, which can be severe enough to lead to discontinuation of the treatment in some patients. Additionally, there are concerns about the long-term safety of these drugs, including potential risks of pancreatitis and thyroid C-cell tumors. Furthermore, in the midst of the profound weight loss lies a looming problem: lean mass loss. Up to 40% of the weight loss with these drugs comes from tissues like muscle and bone. Given all of these problems, it’s little wonder that roughly 70% of people taking these drugs choose to drop the medication within two years. This, of course, creates its own problems—insofar as stopping the drugs results in rapid weight regain, it’s tempting to conclude that most of the weight regain is a result of fat mass, rather than lean mass; the person could have a higher percent body fat than before they ever started the drug.
Enhancing endogenous GLP-1 production through diet
Nevertheless, GLP-1 is clearly a hormone we want to leverage to optimize our metabolic health. Instead of relying on medications, there are dietary strategies to enhance the body’s natural GLP-1 production. Macronutrients, including proteins, certain carbohydrates, and natural fats are potent stimulators of GLP-1 secretion.
Prebiotic fibers and GLP-1
Prebiotic fibers, such as inulin, oligofructose, and other non-digestible carbohydrates, play a crucial role in enhancing GLP-1 secretion. These fibers are found in foods like chicory root, garlic, onions, leeks, asparagus, and bananas. When consumed, prebiotic fibers travel to the large intestine where they are fermented by gut bacteria, producing short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate. These SCFAs stimulate the L-cells in the intestine to release GLP-1.
Research has shown that increasing dietary intake of prebiotic fibers can significantly boost GLP-1 levels. For example, one study found that consuming a diet rich in fermentable fibers improved gut health and increased the release of gut hormones, including GLP-1, which contributed to better appetite regulation and metabolic health.
Yerba mate and GLP-1
Yerba mate, a traditional South American beverage made from the leaves of the Ilex paraguariensis plant, contains several bioactive compounds that can influence GLP-1 secretion. These compounds include chlorogenic acid and ferulic acid, both of which have been studied for its metabolic effects.
Chlorogenic acid, a potent antioxidant found in yerba mate, has been shown to increase GLP-1 secretion. Studies suggest that chlorogenic acid can enhance the release of GLP-1 from the L-cells in the intestine, thereby promoting satiety and reducing food intake. Ferulic acid, another bioactive compound in yerba mate, also contributes to the enhancement of GLP-1 levels. Together, these compounds help in modulating glucose metabolism and appetite.
Regular consumption of yerba mate has been associated with increased GLP-1 levels and improved satiety. For example, a study showed that drinking yerba mate promoted satiety and lowered body weight, in part through stimulation of GLP-1 (Hussein et al., 2011). Additionally, yerba mate’s caffeine content can further enhance these effects by stimulating the central nervous system and potentially increasing energy expenditure.
Conclusion
GLP-1 is a helpful hormone in regulating metabolism and appetite. While GLP-1 receptor agonists are effective in managing type 2 diabetes and obesity, they come with potential side effects. Enhancing endogenous GLP-1 production through diet, including the intake of specific macronutrients, prebiotic fibers, and yerba mate, offers a natural and holistic approach to leveraging the benefits of this hormone. By integrating these dietary strategies, individuals can potentially improve their metabolic health and manage their appetite more effectively.
About the author: Dr. Benjamin Bikman is the director of the Unicity Scientific Advisory Board. He earned his doctorate in bio-energetics and specialized metabolic disorders as a postdoctoral fellow of the Duke-National University of Singapore. As a professor and scientist at Brigham Young University, Dr. Bikman’s focus is understanding chronic, modern-day diseases with an emphasis on the origins and consequences of metabolic disorders, including diabetes and obesity. He frequently publishes his research in peer-reviewed journals and presents at international science meetings.