ACEND

Polyphenols and GLP-1: A Synergistic Approach to Metabolic Health

Polyphenols are nature’s way to boost GLP-1 secretion

January 20, 2025

Contributing Authors: Team TRILITY / ACEND

Polyphenols and GLP-1: A Synergistic Approach to Metabolic Health

Metabolic disorders such as type 2 diabetes, obesity, and metabolic syndrome have become significant public health concerns. Glucagon-like peptide-1 (GLP-1) has emerged as a key therapeutic target due to its role in regulating insulin secretion, appetite control, and glucose metabolism. Recent research highlights the potential of polyphenols, naturally occurring bioactive compounds found in various plant-based foods, to modulate GLP-1 secretion and enhance metabolic health.  In this article we explore how polyphenols interact with GLP-1 pathways, their potential as a GLP-1-friendly therapeutic approach, and their relevance in managing chronic inflammation and metabolic disorders.

Understanding GLP-1 and Its Role in Metabolic Health

GLP-1 is an incretin hormone secreted primarily by enteroendocrine L-cells in the intestine in response to nutrient intake. It plays a critical role in metabolic regulation by:

  • Enhancing insulin secretion in a glucose-dependent manner, reducing the risk of hypoglycemia.
  • Suppressing glucagon release, which prevents excessive glucose production by the liver.
  • Delaying gastric emptying, leading to prolonged satiety and reduced caloric intake.
  • Promoting weight loss through appetite suppression and increased energy expenditure.
  • Exerting neuroprotective and anti-inflammatory effects, which are beneficial for cognitive health.

Given these benefits, pharmaceutical GLP-1 receptor agonists (e.g., semaglutide, liraglutide) have gained widespread use in treating type 2 diabetes and obesity. However, emerging evidence suggests that dietary polyphenols can naturally stimulate GLP-1 secretion and improve metabolic health without the potential side effects of synthetic drugs.

Polyphenols as Natural Modulators of GLP-1 Secretion

Polyphenols exert their effects on GLP-1 secretion through multiple mechanisms, including activation of gut microbiota, modulation of enteroendocrine cells, and interaction with metabolic pathways. Some of the most effective polyphenols in promoting GLP-1 activity include:

1. Quercetin and Dihydroquercetin (Taxifolin)

Quercetin and its metabolite dihydroquercetin have been shown to enhance GLP-1 secretion by stimulating the AMP-activated protein kinase (AMPK) pathway, which plays a central role in cellular energy regulation. Studies indicate that quercetin improves insulin sensitivity and reduces inflammation, further enhancing GLP-1 effectiveness.

2. Epicatechins (Green Tea Polyphenols)

Green tea polyphenols, particularly (-)-epicatechins, have been linked to increased GLP-1 release. These compounds stimulate gut microbiota, particularly Akkermansia muciniphila, a beneficial bacterium associated with improved metabolic health and enhanced GLP-1 secretion.

3. Proanthocyanidins (Grape Seed Extract)

Grape seed-derived proanthocyanidins have been found to modulate gut microbiota and promote the secretion of GLP-1. Their antioxidant and anti-inflammatory properties further support glucose homeostasis and insulin function.

4. Curcumin (CurcuRouge®)

Curcumin, a bioactive compound in turmeric, has demonstrated the ability to enhance GLP-1 secretion by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Additionally, curcumin reduces oxidative stress and chronic inflammation, which are key factors in metabolic dysfunction. The clinically proven enhanced bioavailability of CurcuRouge® in ACEND makes it an effective GLP-1-friendly polyphenol.

5. Luteolin

Luteolin, a flavone found in vegetables and medicinal herbs, influences GLP-1 secretion by modulating the intestinal microbiota and reducing inflammation. It enhances insulin sensitivity and has been shown to protect pancreatic beta cells from oxidative stress.

6. Nigellin™ (Black Cumin Seed Extract)

Black cumin seed extract, rich in thymoquinone, influences GLP-1 secretion by modulating gut microbiota and reducing inflammation. Studies indicate that Nigellin™ enhances insulin signaling and improves glucose metabolism.

Polyphenols, Gut Microbiota, and GLP-1: The Interplay

The gut microbiome plays a crucial role in polyphenol metabolism and GLP-1 secretion. Many polyphenols are poorly absorbed in their native form but are metabolized by gut bacteria into bioactive metabolites that stimulate GLP-1 secretion. Key microbial pathways include:

  • Enhancing short-chain fatty acid (SCFA) production: Polyphenols promote the growth of SCFA-producing bacteria such as Bifidobacterium and Lactobacillus. SCFAs like butyrate and propionate directly stimulate L-cells to secrete GLP-1.
  • Modulating bile acid metabolism: Polyphenols influence bile acid composition, which interacts with the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) to enhance GLP-1 secretion.
  • Inhibiting inflammation: Chronic inflammation disrupts GLP-1 signaling. Polyphenols reduce inflammatory cytokines such as TNF-α, IL-6, and CRP, thereby preserving GLP-1 function.

Metabolites of Polyphenols and Their Role in GLP-1 Activity

When polyphenols are broken down by gut microbiota, they generate bioactive metabolites that further enhance GLP-1 activity. Examples include:

  • Urolithins (from ellagitannins in pomegranates and nuts): These compounds influence mitochondrial function and metabolic pathways that support GLP-1 secretion.
  • Enterolactone (from lignans in flaxseeds): It enhances gut hormone secretion and promotes glucose metabolism.
  • Dihydroresveratrol (from resveratrol metabolism): This metabolite improves insulin sensitivity and contributes to GLP-1 activity.

Clinical Implications and the Role of ACEND

ACEND, as a medical food designed to combat chronic inflammation and metabolic dysfunction, incorporates GLP-1-friendly polyphenols with high bioavailability. By leveraging clinically validated polyphenols such as CurcuRouge®(bioavailable curcumin), grape seed proanthocyanidins, green tea epicatechins, and quercetin, ACEND supports natural GLP-1 secretion while addressing inflammation, insulin resistance, and gut microbiome health.

Unlike pharmaceutical GLP-1 agonists, which may have gastrointestinal side effects and require long-term injections, polyphenols provide a drug-free therapeutic alternative with broader metabolic benefits. Their ability to modulate gut microbiota, reduce oxidative stress, and enhance insulin function makes them an essential component in the prevention and management of metabolic diseases.

Conclusion

Polyphenols represent a powerful, GLP-1-friendly approach to metabolic health. Their ability to enhance natural GLP-1 secretion through gut microbiota modulation, anti-inflammatory pathways, and bioactive metabolites positions them as a promising alternative or complement to traditional GLP-1 therapies. ACEND, with its scientifically curated blend of bioavailable polyphenols, serves as an effective medical food for individuals seeking to optimize GLP-1 function, combat chronic inflammation, and improve metabolic health.

References

  1. Dehghanian, F., et al. (2023). “Polyphenols and their role in GLP-1 secretion: A metabolic perspective.” Nutrients, 15(2), 312.
  2. Wang, X., et al. (2022). “Flavonoids and gut microbiota: Interactions that influence metabolic health and GLP-1 activity.” Frontiers in Nutrition, 9, 982374.
  3. Liu, Y., et al. (2021). “Curcumin and GLP-1 secretion: Evidence from metabolic and gut microbiota studies.” Journal of Functional Foods, 87, 104756.
  4. Li, C., et al. (2023). “The role of green tea polyphenols in metabolic health via GLP-1 modulation.” Molecular Nutrition & Food Research, 67(5), 2200917.
  5. Sun, H., et al. (2023). “Gut microbiota-derived polyphenol metabolites and their impact on GLP-1 secretion.” Cell Metabolism, 35(1), 124-138.

Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.