Dose-response Effect of Pine Nut Oil as a Dual FFA1 and FFA4 Agonist on Glucose Tolerance in Healthy Humans.

NCT03305367 | Completed

• 1 other identifier: PINO3
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Several free fatty acids receptors (FFARs) have been discovered. These have been implicated in metabolic processes and inflammation. Consequently, these receptors have attracted interest as targets for the treatment of metabolic and inflammatory diseases, including obesity and type 2 diabetes. Two of these FFARs (FFA1, FFA4), which is activated by specific free fatty acids (FFAs), is expressed on enteroendocrine cells, pancreatic beta-cells and adipocytes. They have been linked to 1) increased glucagon-like peptide-1 (GLP-1) secretion and hence the incretin-mediated increase in glucose-stimulated insulin secretion (GSIS) and suppression of glucagon secretion, 2) a direct positive effect on GSIS, 3) reduced inflammation and 4) improved insulin sensitivity. These functions and the abundance of fatty acids in food suggest that FFARs can be considered as nutrient sensing regulators of metabolism. Roux-en-Y gastric bypass (RYGB), frequently results in immediate beneficial effects on glucose metabolism and often complete remission of type 2 diabetes. This may in part be explained by increased GLP-1 levels after surgery. It appears that the effect depends on nutrient delivery directly to the lower parts of the small intestine. It is possible that the RYGB effects are partly due to enteroendocrine stimulation of FFA1 and perhaps FFA4 by direct nutrient delivery, i.e. FFA release in the lower intestines. Pinolenic acid from pine nuts has been shown to be a potent dual FFA1/FFA4 agonist. Based on these findings the investigators have planned a number of human intervention studies in order to investigate 1) the optimal oral formulation of pine nut oil 2) whether it is possible to mimic the beneficial effects observed after RYGB, 2) if it is possible to increase GLP-1 secretion by stimulating FFA1/FFA4 on enteroendocrine cells causing improved GSIS and increased satiety and 3) enhancement of GSIS by directly stimulating FFA1 on beta-cells.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (6)

• Blood glucose

  Area under the curve of blood glucose

  4 hours OGTT

• Insulin and C-peptide

  Area under the curve of Insulin and C-peptide

  4 hours OGTT

• Incretins

  Area under the curve of incretins

  4 hours OGTT

• ghrelin

  Area under the curve of ghrelin

  4 hours OGTT

• appetite

  Visual analog scale - area under the curve

  4 hours OGTT

• Gastrointestinal tolerability

  Visual analog scale -mm

  4 hours OGTT

Study Arms (3)

Screening/Baseline

NO INTERVENTION

A standard OGTT with no supplementation/intervention

Hydrolyzed pine nut oil low dose

EXPERIMENTAL

Standard OGTT supplemented with 3 g of hydrolyzed pine nut oil

Dietary Supplement: Hydrolyzed pine nut oil

Hydrolyzed pine nut oil high dose

EXPERIMENTAL

Standard OGTT supplemented with 6 g of hydrolyzed pine nut oil

Dietary Supplement: Hydrolyzed pine nut oil

Interventions

Hydrolyzed pine nut oil DIETARY_SUPPLEMENT

Randomized cros-over intervention of 3 OGTT with no oil, low dose or high dose.

Hydrolyzed pine nut oil high dose; Hydrolyzed pine nut oil low dose

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Southern Denmark: collaborator

Study Sites (1)

Department of Endocrinology

Odense, 5000, Denmark

Location

Related Publications (1)

• Sorensen KV, Korfitzen SS, Kaspersen MH, Ulven ER, Ekberg JH, Bauer-Brandl A, Ulven T, Hojlund K. Acute effects of delayed-release hydrolyzed pine nut oil on glucose tolerance, incretins, ghrelin and appetite in healthy humans. Clin Nutr. 2021 Apr;40(4):2169-2179. doi: 10.1016/j.clnu.2020.09.043. Epub 2020 Oct 2.

  PMID: 33059911 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Kurt Højlund, MD

  Department of Endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MSc, PhD-student

Model Details: Subjects complete three oral glucose tolerance tests (OGTT) on different days, with a minimum of one week in between. First visit is a combined screening and baseline OGTT, with no supplementation. At the second and third visit subjects are randomly assigned to either 3 g of hydrolyzed pine nut oil or 6 g of hydrolyzed pine nut oil.

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 9, 2017
• Study Start: February 6, 2017
• Primary Completion: August 23, 2017
• Study Completion: August 23, 2017
• Last Updated: December 13, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)