The research was published recently in the journal Biomolecules. The authors are associated with several hospitals and research institutes in Tarragona, Spain.
Do flavonols stimulate intestinal cells directly?
The researchers’ goal was to determine the effect of the many constituents of a so-called grape seed proanthocyanidin extract (GSPE) on the release of several enterohormones in various portions of the gut. The ingredient was obtained from Les Dérivés Résiniques et Terpéniques (Dax, France - newly part of the Firmenich group), and was said to be a source of flavan-3-ols compounds including catechin and epicatechin monomers and their respective oligomers. Some of the compounds found in the extract are not absorbed and pass through the intestine to reach the colon, where they are metabolized.
The researchers noted that grape seed extract has been previously studied for its effects on appetite control and controlling metabolic syndrome. But there has been little understanding of the mechanisms of action for these effects, though modification of the endocrine system has been suggested as a possibility.
They also observed that past studies in rats, pigs and humans have found that some of the constituents of GSPE persist in the gut and/or pass through undigested to be found in feces. Could these undigested, unchanged portions of the extract, which in the past might have been considered as mere waste material, be stimulating the epithelial cells in some way?
“Thus, not only the polyphenol’s metabolites, but also some of the original compounds found in GSPE may interact with the enteroendocrine cells that are distributed along the gastrointestinal tract,” the authors wrote.
Novel test array used
To test this theory, the authors used a novel experimental array consisting of pig intestines mounted into a device. The test array was described in a 2018 paper published in the Journal of Agricultural Food Chemistry. Pig intestines and the animal’s metabolism are a very similar model to that of humans, and for obvious reasons large sections of functioning pig intestines are easier to obtain than are human examples.
The researchers were, however, able to test their theory in portions of human intestines. They obtained 17 samples (12 male and 5 female) of human intestines from older individuals that had been excised during surgery. These intestinal cells were stimulated with the GSPE test material in a different way because the intestinal sections were not complete enough to mount into the novel test array.
The researchers found evidence that certain whole constituents—not metabolites—of GSPE directly stimulated the release of specific appetite control hormones by the enteroendocrine cells found in the gut. They also found that these results are specific to the location in the gut being discussed.
“In the duodenum, luminal stimulation with procyanidin dimer B2 increased PYY (pancreatic peptide YY) secretion, but not CCK secretion, while catechin monomers (catechin/epicatechin) significantly increased CCK (cholecystokinin) release, but not PYY release. The differential effects of GSPE and its pure compounds on enterohormone release at the same intestinal segment suggest that they act through chemosensors located apically and unevenly distributed along the gastrointestinal tract,” the authors concluded.
Results could help direct product development
Commenting independently on the study, James Kennedy, PhD, principal in the consulting firm Functional Phenolics LLC, said this new research sheds additional light on the satiation feedback loop between the brain and the gut that helps control food intake. The research could be a building block in the development of better targeted and more effective appetite control products. Dr Kennedy has worked with and studied grape seed extracts for decades, including previously being President of Polyphenolics.
“The consumption of food and its control is modulated in part by the enteroendocrine system. Homeostasis depends on effective communication between our digestive system and our brain and it is generally accepted that many chronic diseases have their origin in the dysfunction of this feedback system,” Kennedy told NutraIngredients-USA.
“The findings in this paper provide wonderful evidence that flavanols can exert their bioactivity by acting directly with the digestive system and stimulating the enteroendocrine system and increase the production of anorexigenic peptides. While flavanols have long been considered to have a role in food intake management, this direct evidence for activity on the enteroendocrine system represents an important step in development,” he added.
2020 Jun 1;10(6):E844. doi: 10.3390/biom10060844
Effects of Flavanols on Enteroendocrine Secretion
Authors: Grau-Bové C, et al.
Editor's Note: An earlier version of this article did not mention that the ingredient was supplied by DRT. We apologize for the omission.