Pomegranate juice, but not an extract, confers a lower glycemic response on a high–glycemic index food: randomized, crossover, controlled trials in healthy subjects

• Published in: The American journal of clinical nutrition Vol. 106; no. 6; pp. 1384 - 1393
• Main Authors: Kerimi, Asimina, Nyambe-Silavwe, Hilda, Gauer, Julia S, Tomás-Barberán, Francisco A, Williamson, Gary
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2017; American Society for Clinical Nutrition, Inc
• Subjects: Acarbose; acute effects; Adult; alpha-amylase; Animals; Area Under Curve; Beverages; Blood; blood glucose; Blood Glucose - metabolism; Blood levels; Bread; breads; Caco-2 Cells; carbohydrate digestion; Citric acid; clinical nutrition; Cross-Over Studies; Diabetes; Diabetes mellitus; Diet; Dietary supplements; Double-Blind Method; drugs; Fruit; Fruit and Vegetable Juices; Fruit juices; fruits; Gastrointestinal Microbiome; Glucose; Glucose transport; Glucose transporter; Glucose Transporter Type 2 - metabolism; glucose transporters; glycemic effect; Glycemic index; Glycemic Index - drug effects; Glycemic Load - drug effects; Hep G2 Cells; Humans; Hydrolyzable Tannins - pharmacology; Hypoglycemic Agents - pharmacology; Indexing; Intestinal microflora; intestinal microorganisms; Lythraceae - chemistry; Metabolism; Metabolites; Microbiota; Microorganisms; noninsulin-dependent diabetes mellitus; Nutrient deficiency; Oocytes; pH effects; Plant Preparations - pharmacology; polyphenol; Polyphenols; Polyphenols - pharmacology; pomegranate juice; pomegranates; Postprandial Period; Randomization; Risk assessment; Risk reduction; starch; Sugar; Xenopus; Young Adult; α-Amylase; glucose transport; glycemic index; carbohydrate digestion; starch; polyphenol
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.117.161968

Low–glycemic index diets have demonstrated health benefits associated with a reduced risk of developing type 2 diabetes. We tested whether pomegranate polyphenols could lower the glycemic response of a high–glycemic index food when consumed together and the mechanism by which this might occur. We compared the acute effect of a pomegranate juice and a polyphenol-rich extract from pomegranate (supplement) on the bread-derived postprandial blood glucose concentration in 2 randomized, crossover, controlled studies (double-blinded for the supplements), each on 16 healthy volunteers. An additional randomized, crossover, controlled study on 16 volunteers consuming constituent fruit acids in a pH-balanced solution (same pH as pomegranate) and bread was conducted to determine any contributions to postprandial responses caused by acidic beverages. As primary outcome, the incremental area under the curve for bread-derived blood glucose (−33.1% ± 18.1%, P = 0.000005) and peak blood glucose (25.4% ± 19.3%, P = 0.0004) were attenuated by pomegranate juice, compared with a control solution containing the equivalent amount of sugars. In contrast, the pomegranate supplement, or a solution containing the malic and citric acid components of the juice, was ineffective. The pomegranate polyphenol punicalagin was a very effective inhibitor of human α-amylase in vitro, comparable to the drug acarbose. Neither the pomegranate extract nor the individual component polyphenols inhibited 14C-D-glucose transport across differentiated Caco-2/TC7 cell monolayers, but they inhibited uptake of 14C-glucose into Xenopus oocytes expressing the human glucose transporter type 2. Further, some of the predicted pomegranate gut microbiota metabolites modulated 14C-D-glucose and 14C-deoxy-D-glucose uptake into hepatic HepG2 cells. These data indicate that pomegranate polyphenols, when present in a beverage but not in a supplement, can reduce the postprandial glycemic response of bread, whereas microbial metabolites from pomegranate polyphenols exhibit the potential to further modulate sugar metabolism much later in the postprandial period. This trial was registered at clinicaltrials.gov as NCT02486978, NCT02624609, and NCT03242876.