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Polyphenols as Natural Inhibitors of DPP-4 and Their Role in Enhancing GLP-1 Activity

Polyphenols are GLP-1 boosters due to their ability to inhibit DPP-4. Read on to understand…

January 20, 2025

Contributing Authors: Team TRILITY / ACEND

Polyphenols as Natural Inhibitors of DPP-4 and Their Role in Enhancing GLP-1 Activity

In recent years, glucagon-like peptide-1 (GLP-1) has gained significant attention for its role in regulating blood sugar levels and supporting metabolic health. GLP-1 is an incretin hormone produced in the intestines in response to food intake, stimulating insulin secretion while suppressing glucagon release. However, its effects are short-lived due to rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), limiting its ability to help regulate blood sugar effectively (Gulati & Singh, 2017).

A growing body of research suggests that certain polyphenols—bioactive compounds found in plants—naturally inhibit DPP-4, extending the half-life of GLP-1 and improving insulin response. This article explores how polyphenols function as natural DPP-4 inhibitors and their potential impact on metabolic health.

Understanding the Role of DPP-4 in GLP-1 Regulation

DPP-4 is an enzyme responsible for degrading GLP-1 and another key incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). By cleaving these hormones, DPP-4 significantly reduces their ability to stimulate insulin release, which can lead to impaired glucose metabolism (Kawser et al., 2019).

DPP-4 inhibitors are commonly prescribed for individuals with type 2 diabetes to prevent the degradation of GLP-1, allowing it to remain active for longer periods. However, certain naturally occurring polyphenols found in food may have similar inhibitory effects on DPP-4, offering a diet-based approach to supporting GLP-1 activity.

Polyphenols as Natural DPP-4 Inhibitors

Polyphenols are naturally occurring compounds with strong antioxidant and anti-inflammatory properties found in fruits, vegetables, tea, coffee, and wine. Several studies have demonstrated their potential in inhibiting DPP-4 activity, which enhances GLP-1 secretion and insulin sensitivity (Zhu et al., 2020).

How Polyphenols Inhibit DPP-4

Research suggests that polyphenols can bind to the active site of DPP-4, preventing it from interacting with and degrading GLP-1. This mechanism effectively prolongs the half-life of GLP-1, allowing for sustained insulin secretion and better glucose control (Bruckbauer & Zemel, 2018).

Dietary Sources of Polyphenols with DPP-4 Inhibitory Activity

Including polyphenol-rich foods in the diet can naturally enhance GLP-1 levels and improve metabolic function. Some of the most well-researched polyphenol-rich foods that have shown potential DPP-4 inhibitory properties include:

  • Grape Seed Extract – Contains proanthocyanidins, which have been shown to modulate gut microbiota and improve insulin sensitivity (Zhu et al., 2020).
  • Green Tea – Rich in epigallocatechin gallate (EGCG), a compound found to enhance GLP-1 secretion and reduce glucose levels (Bruckbauer & Zemel, 2018).
  • Berries – Blueberries, strawberries, and raspberries contain anthocyanins, which have demonstrated DPP-4 inhibitory activity in animal studies.
  • Cocoa and Dark Chocolate – High in flavonoids, which contribute to improved glucose metabolism and insulin signaling.
  • Onions and Apples – These foods are rich in quercetin, a well-known polyphenol that exhibits DPP-4 inhibitory effects (Sheng et al., 2019).

By regularly consuming these foods, individuals may naturally support their GLP-1 activity and improve overall blood sugar control.

Potential Benefits for Type 2 Diabetes and Metabolic Health

Given their ability to inhibit DPP-4, polyphenols offer several metabolic health benefits, particularly for individuals managing type 2 diabetes or prediabetes:

  1. Enhanced Insulin Secretion – By prolonging GLP-1 activity, polyphenols help stimulate insulin release in response to meals (Kawser et al., 2019).
  2. Improved Blood Sugar Control – Higher GLP-1 levels reduce blood sugar fluctuations, supporting more stable glucose metabolism (Sheng et al., 2019).
  3. Weight Management – Some polyphenols regulate appetite and satiety hormones, which may help with weight loss or preventing obesity-related insulin resistance (Zhu et al., 2020).
  4. Reduced Inflammation – Many polyphenols possess anti-inflammatory properties, which can help mitigate chronic inflammation linked to metabolic disorders (Gulati & Singh, 2017).

How to Incorporate More Polyphenols Into Your Diet

To take advantage of polyphenols’ DPP-4 inhibitory properties, consider adding more of the following foods into your daily routine:

  • Drink green tea instead of sugary beverages.
  • Snack on berries, apples, or nuts rather than processed snacks.
  • Use spices like turmeric, cinnamon, and black cumin, which also contain bioactive polyphenols.
  • Choose dark chocolate (70% or higher cocoa content) for a healthy indulgence.
  • Include grape seed extract or quercetin supplements if dietary intake is insufficient (with guidance from a healthcare provider).

Conclusion

Scientific research continues to uncover the power of polyphenols as natural DPP-4 inhibitors, highlighting their potential to support GLP-1 activity and improve metabolic health. While pharmaceutical DPP-4 inhibitors are widely used for diabetes management, incorporating polyphenol-rich foods into the diet presents a natural, food-based approach to enhancing GLP-1 levels and blood sugar control.

For those looking to support healthy glucose metabolism naturally, increasing the intake of polyphenol-rich foods may be a beneficial strategy—one that aligns with the growing food-as-medicine movement.

References

  1. Gulati, P., & Singh, N. (2017). “Dipeptidyl peptidase-4 inhibitors: Anti-diabetic drugs with multiple therapeutic potential.” Phytomedicine, 23(11), 1077-1085.
  2. Zhu, W., Jia, Q., Wang, Y., Zhang, Y., & Xia, M. (2020). “The polyphenol-rich extract from grape seed attenuates insulin resistance and modulates gut microbiota in type 2 diabetic mice.” Food & Function, 11(3), 2408-2421.
  3. Kawser, H. M., Kabir, N., Berzina, I., & Venskutonis, P. R. (2019). “Dietary polyphenols as a safeguard against type 2 diabetes mellitus: A review of their molecular mechanisms.” International Journal of Molecular Sciences, 20(19), 4873.
  4. Bruckbauer, A., & Zemel, M. B. (2018). “Effects of epigallocatechin gallate on glucose metabolism and GLP-1 secretion in human subjects.” Journal of Nutritional Biochemistry, 57, 71-77.
  5. Sheng, J., Guo, L., Ma, J., & Xu, Y. (2019). “Polyphenols and their role in diabetes management: A review of the mechanistic aspects.” International Journal of Food Sciences and Nutrition, 70(4), 417-425.

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