The Gut-Brain Axis Regulates Appetite and Satiety

The postprandial release of glucagon-like peptide 1 (GLP-1) from the intestinal neuroendocrine cells leads to reduced appetite and inhibition of food intake. Vickers et al. note, “GLPs are known to modify food intake, increase satiety, delay gastric emptying and suppress glucagon release. (1)”

Clinically, one can enhance gastrointestinal (GI) derived GLP signaling by optimizing upper GI hydrochloric acid (HCl) secretion (or by supplementing HCl), enhancing parasympathetic tone (e.g., vagal nerve innervation), and by employing a high-protein diet (2). A recent human study by Geraedts et al. assaying a biopsy of intestinal duodenal tissue found that pea protein most powerfully stimulated both cholecystokinin (CCK) and GLP-1, suggesting that pea protein should be the protein of choice for weight loss and appetite control (3).

For this application, I like pea protein powder. This ultra-clean, hypoallergenic protein is rich in the anabolic amino acids leucine and glutamine as well as taurine, glycine, and arginine. Unlike soy or whey protein powders, yellow pea is low in potential allergens in lectins, making it a suitable meal replacement.

What about plant based polyphenols and GLP-1?

Preliminary research by Dao et al. indicates that part of resveratrol’s beneficial metabolic and anti-diabetic effects may occur through the same mechanism we discussed above, optimizing the “enteroendocrine axis” and thereby influencing blood-sugar regulation and appetite (4). Treatment with resveratrol for five weeks in high-fat-diet-induced diabetic mice was found to increase GLP-1, improve oral glucose tolerance, and reduce inflammation in peripheral tissues via the increased production of the anti-inflammatory cytokine IL-10. This is consistent with a human clinical trial by Ghanaim et al. reporting that 100 mg of resveratrol given prior to a high-fat, high-carbohydrate meal offset postprandial elevations in gut-derived endotoxin (5). When choosing a resveratrol product, it’s ideal to find is a unique blend of resveratrol alongside other naturally accuring stilbenes pterostilbene and the antioxidant quercetin.

Does it seem wise to use DPP4 enzymes?

Given that GLP-1 is an important gut-metabolic hormone that is dysregulated in a large percentage of the population, does it seem wise to ingest digestive enzymes containing DPP4 enzyme, which is known to break down GLP-1 (6). Moreover a plethora of pharmaceutical agents designed to increase GLP-1 signaling via inhibiting the DPP4 enzyme- such as sitagliptin, vildagliptin, and saxagliptin – have demonstrated clinical success in the ameliorating deranged insulin control in type 2 diabetic patients. Thus I feel that it is unwise to supplement with digestive enzymes containing DPP4.

Copyright 2012 Phillips et al. Update on incretin hormones











1)  Vickers MH. Developmental programming of the metabolic syndrome – critical windows for intervention. WJD. 2011;2(9):137.

2) De Silva A, Salem V, Long CJ, et al. The Gut Hormones PYY3-36 and GLP-17-36 amide Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans. Cell Metabolism. 2011.

3)  Geraedts MCP, Troost FJ, Tinnemans R, et al. Release of satiety hormones in response to specific dietary proteins is different between human and murine small intestinal mucosa. Ann. Nutr. Metab. 2010;56(4):308-313.

4) Dao et al 2011. Dao T-MA, Waget A, Klopp P, et al. Resveratrol increases glucose induced GLP-1 secretion in mice: A mechanism which contributes to the glycemic control. PLoS ONE. 2011;6(6):e20700.

5) Ghanim, H. A Resveratrol and Polyphenol Preparation Suppresses Oxidative and Inflammatory Stress Response to a High-Fat, High-Carbohydrate Meal. Endocrinology 2011. 152(3 ). 1193-1194

6) Phillips, L. K., & Prins, J. B. (2012). Update on incretin hormones. Annals of the New York Academy of Sciences, Update on incretin hormones, 1243(1), E55–E74. doi:10.1111/j.1749-6632.2012.06491.x

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